5/25/2018 1-s2.0-S0012160699993405-main

1/20

REVIEW

Comparative Biology of Calcium Signaling duringFertilization and Egg Activation in Animals

Stephen A. Stricker1

D epartm ent of Bio logy, U n iv ersi t y of N ew M exico, Al buqu erque, N ew M exico 87131

During animal fertilizations, each oocyte or egg must produce a proper intracellular calcium signal for development t

proceed normally. As a supplement to recent synopses of fertilization-induced calcium responses in mammals, this papereviews the spatiotemporal properties of calcium signaling during fertilization and egg activation in marine invertebrateand compares these patterns with what has been reported for other animals. Based on the current database, fertilizatiocauses most oocytes or eggs to generate multiple wavelike calcium oscillations that arise at least in part from the releasof internal calcium stores sensitive to inositol 1,4,5-trisphosphate (IP3). Such calcium waves are modulated by upstreampathwaysinvolvingoolemmal receptorsand/orsolublesperm factorsandin turnregulatecalcium-sensitivetargetsrequirefor subsequent development. Both protostome animals (e.g., mollusks, annelids, and arthropods) and deuterostomes(e.g., echinoderms and chordates) display fertilization-induced calcium waves, IP3-mediated calcium signaling, and thability to use a combination of external calcium influx and internal calcium release. Such findings fail to support thdichotomy in calcium signaling modes that had previously been proposed for protostomes vs deuterostomes and insteasuggest that various features of fertilization-induced calcium signals are widely shared throughout the animakingdom. 1999Academic Press

K ey W o r d s : calciumwave;CICR; calciumoscillations;oocyte;meiosis arrest;maturation;spermfactor;ICSI;IP3;cADP

IP3R; RyR; capacitative calcium entry; CaMKII; mouse; sea urchin; protostome; deuterostome.

INTRODUCTION

D uring ferti l ization, anim al oocyt es or eggs m ust un dergo

a proper chan ge in their int racellular free calcium levels

([C a 2]i) t o ensur e t ha t developm ent proc eeds nor m a l l y

(Epel, 1990; N uccitelli, 1991; Whit aker and Sw ann , 1993).

In t he c a s e of m a m m a l s , t he c ha r a c t er i s t i c pr oper t i es of

fert i l i za t i on-i nduc ed c a l c i um s i gna l i ng ha v e b een t hor -

oughl y desc ri b ed (S wa nn a nd Ozi l , 199 4; Y a na gim a c hi ,

1994; Miyazaki, 1995; Schultz and Kopf, 1995; Kline, 1996;

BenYosef and Shalgi, 1998; Ozil, 1998). H ow ever, to gain a

broader perspective, this review compares the spatiotempo-

ral patterns of calcium signals during normal fertilization or

artifi cial activat ion in ma rine invertebrates w here calcium

levels have been directly monitored in oocytes or eggs (i.e.,

in fema le gametes before or after the completion of m eiotic

maturation). In addition, the contributions of external cal-

c i um i nfl ux a nd i nt erna l c a l ci um r el ea s e a r e a s sess ed i n

order to reevaluate the hypothesis that in an imals in w hich

t he a dul t m out h dev elops from t he em b ry oni c b l a s t opor

(i .e., protostom es ) fundam entally different mechan ism

of generating calcium transients are employed during fer

t i l i za t i on t ha n a r e used i n deut er os t om es , w hi c h do no

derive th eir m outh from th e blast opore (Jaffe, 1983, 1985

The group-by-group synopsis is organized according to

traditional phylogeny of invertebrates (Pearse et al ., 1987a nd i s s ub s eq uent l y s y nt hes ized w i t h r epresent a t i v e da t

ob t a i ned fr om ot her a ni m a l s w i t h t he a i m of a ddress i ng

key question in developm ental biology: nam ely, wh at kind

of calcium signals are used by animal oocytes and eggs t

trigger norma l development?

CNIDARIA

During ferti l ization in hydrozoan jellyfi sh (Phylum Cni

daria, Class Hydrozoa), the egg generates a single calcium

transient of undetermined spatial properties (Freeman an

Ridgw ay, 1993) (Table 1; Fig. 1A). Althou gh th e sources o

c a l ci um m ob i l ized dur i ng fert i l i za t i on ha v e not b een d1 Fax: (505) 277-0304. E-mail: sstr@unm.edu.

D evelopm ental Biology 211, 157176 (1999)

Article ID dbio.1999.9340, availa ble online at h tt p://w w w .idealibrary.com on

0012-1606/99 $30.00

Copyright 1999 by Academic Press

All rights of reproduction in any form reserved. 157

5/25/2018 1-s2.0-S0012160699993405-main

2/20

5/25/2018 1-s2.0-S0012160699993405-main

3/20

rectly evaluated, calcium release from internal stores may

play a role, since calcium ionophore can trigger a calcium

t r a ns ient i n unfer t i li zed eggs i nc uba t ed i n c a l ci um -free

seaw at er (C aFSW) (Freem an and Ridgw ay, 1987). M oreover,

t he m a t ur e eggs of c ni da r ia ns exhi b it a c a l c ium t r a ns ient

w hen injected w ith inosit ol 1,4,5-trisphosphate (IP 3) (Free

man and Ridgway, 1991) but not when treated with exces

potassium (Freeman and Ridgwa y, 1993), w hich stimulat e

e x t er n a l c a l c iu m i n fl u x t h r o u gh v o l t a ge -g a t e d c a l c iu m

channels in the plasmalemma (Conley and Brammer, 1998)

FIG. 1. Temporal patt erns of fertilization-induced calcium signals in protostom e (BF) vs deuterostom e (G L) anim als [note: cnidarian

(A)a re not readily a llied w ith either lineage (Pearseet al., 1987)]. N ormal state of oocyt e m aturation at fertilization: prophase I-arrested (D

F); betw een germina l vesicle breakdow n and polar body format ion (H); met aphase I-arrested (B, C , E, I); met aphase II-arrested (JL

pronuclear egg (A, G ). Amplitudes, durations, and frequencies of calcium transients are not draw n t o scale, and th e t im ings of fi rst cell cy cl

events are only approxima te (for pertinent data, see Table 1 and text). C alcium traces and cell cycle ch ronology are based on (A) Freema

an d Rid gw ay (1991, 1993); (B) Stri cker (1996b); (C ) Togoet al. (1993), D eguchi and Osan ai (1994b); (D ) G eilenkirchen et al.(1977), D eguch

and Osanai (1994a); (E) Harvey (1939), Eckberg and Miller (1995); (F) G ould and Stephano (1996), Stephano and G ould (1997); (G ) Shen anBuck (1993), Wildi ng et al .(1996); (H) St rick er (1995); (I) Speksni jderet al .(1989), M cD ougall and Levasseur (1998); (J) Ridgw ay et al.(1977

Fluck e t a l . (1991), Abraham e t a l . (1993) for t he medaka O r y z i a s (w hich forms t he s econd pola r body 15 min pos t fert i l iza t ion a n

generates slow calcium waves along the cleavage furrow prior to fi rst cleavage at 90 min postfertilization), Creton e t a l . (1998) for th

zebrafi sh D a n i o (w hich undergoes fi rst cleavage 45 m in postfertilizat ion); (K) Busa and N uccitelli (1985), Keatin g e t a l . (1994); and (L

Tombes et a l . (1992), Jones et a l . (1995a) for the mouse M u s.

15Fert i l i zat i on-Induced C a2 Signals

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

4/20

FIG. 2. Spatial properties of fertilization -induced calcium signals in protostom es (nemertean w orms: AE) vs deuterostom es (starfi sh: F

G ), show ing pseudocolored im ages (AC , F, G ) of ratioed confocal data from C alcium G reen-loaded specimens exam ined every 5 s. Blue

encode low calcium levels, whereas yellows and reds correspond to higher calcium levels. (A) Two mature oocytes from the nemertean

Micrura a laskensis . A s ynchronous ly propa ga t ed cort ica l fl a s h (a rrow hea ds) a r ises from ext erna l ca lcium infl ux a t t he ons et o

fertilization in each oocyt e. First frame is before sperm addit ion; second frame is at 105 s after sperm addit ion, and each subsequent fram

of t he 11-frame sequence is t aken a t 5-s int ervals. (B) Tw o fertilizat ion-induced calcium w aves (arrows) arising 5 a n d 1 0 m i n a f t e

ins emina t ion in t heM . alask ensisoocyte previously show n generating a cortical fl ash in the top row of A. (C )Fertilization-induced calcium

t ra ns ient s in a n imma t ure oocyt e (t op t w o row s ) a nd a ma t ure oocyt e (bot t om row ) of t he nemert ea n Cerebratulus lacteus. N o t e t h

non-w avelike propagation patt erns (arrowheads) in the im ma ture oocyte vs the point-source calcium w ave (arrow) in the m ature specimen

160 Stephen A . Str ick e

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

5/20

Thus, ferti l ization m ay involve calcium release modulat ed

by IP 3 receptors (IP 3Rs) (Berridge, 1993; Bezprozvan ny and

Ehrlich, 1995), w hich presuma bly occur m ainly on t he eggs

endoplasmic reticulum (ER) (Han and Nu ccitelli , 1990).

However, i t remains to be determined (i) i f the ER of cni-

da r ia n eggs a l s o c ont a i ns func t i ona l r y a nodi ne r ec ept ors

(RyRs) (Sorrentino, 1996), the second major class of cal-

cium channel receptors used by cells to mobilize internalcalcium stores (Table 2); an d (ii) w heth er either or bot h o f

these receptor types actually contribute to a normal ferti l-

ization response.

NEMERTEA

Ful l y grow n ooc y t es of t he nem er t ea n w orm Cerebratu-l u s arrest at metaphase I and upon insemination generatemultiple calcium transients for 75 min (Stricker, 1996b;

Fig. 1B). The fi rst ferti l ization-induced calcium transient

comprises an essential ly syn chronous cortical fl ash that

i s m i m i ck ed b y e xc es s p o t a ss iu m o r e l im i n a t ed b y t h e

calcium channel blocker cobalt chloride, collectively sug-

gesting a dependence on external calcium infl ux (Stricker,

1996b). After the cortical fl ash, fertilized oocytes produce

10 calcium w aves that init ial ly arise near the sperm entry

s i t e (S t ri c ker , 19 96b ). S ubs eq uent l y , t he w a v es t end t o

originate from the vegetal hemisphere and do not require

external calcium, since th ey persist in C aFSW (Stricker,

1996b). Although u nfertilized oocy tes can m obilize calcium

w hen treated with ryanodine to stimulate RyRs, fertilization-

induced calcium waves appear to depend on IP 3-mediated

calcium release, given that they are disrupted by heparin

(Stricker, 1996b), w hich is a som ew hat selective inhibitor ofIP 3Rs (Hill et al ., 1987).

A c o rt i c al fl a s h a n d w a v el ik e o sc il la t i on s a l so o cc u r

w hen m ature oocytes of ot her nemertean species are ferti l-

ized (Figs. 2A and 2B). By contrast, prophase-arrested imma-

ture oocytes of C erebratu l us remain uncleaved after sperma ddi t i on a nd genera t e l ow-a m pl i t ude, non-w a v eli ke c a l -

cium t ransients for only 25 min, presumably because th e

o o cy t e s ER h a d n o t f u ll y m a t u r ed b ef or e i n s em i n a t i on

(Stricker et al ., 1998) (Figs. 2C 2E).

MOLLUSCA

O o c y t es pr od u ce d b y c la m s a n d t h e ir a l li es (P h y l u m

M ol l usc a , C l a s s Bi v a l v ia ) a r rest a t eit her propha s e I o

meta phase I and typically un dergo 515 calcium transient

after insemination (Deguchi and Osanai , 1994b; Fig. 1C)

a l t hough fer t i l i zed ooc y t es of t he b i v a l v e M a c t r a displa

onl y a s ingl e c a lc i um t r a ns ient fol l owed b y a n elev a t eplateau (Deguchi and Osanai , 1994a; Fig. 1D). The initia

ferti l ization-induced calcium transient of Rudi tapes a nM y t i l u s arises synchronously around the oocyte as a cortical fl ash that lacks a point-source origin (Abdelmajid et al

1993; Deguchi and Osanai, 1994b). In M y t i l u s, the corticafl a s h i s el i m i na t ed b y t he c a l ci um c ha nnel b l oc ker m e

t hoxy v era pa m i l , i ndic a t i ng t ha t ext erna l c a l c ium i nfl u

occurs at the onset of ferti l ization (Deguchi et al ., 1996C onversely, subsequent calcium oscillations generated in

M y t l i u s oo cy t e s c on t i n u e t o o cc u r i n t h e pr es en c e ometh oxyverapam il (D eguchi et al., 1996) or after t ransfer tC aFSW (D eguchi and Osanai , 1994b), and such postfl as

oscillations are blocked in heparin-loaded oocytes, suggest

i n g a l a t er d epe n de n ce o n IP 3-mediated calcium releas

(Deguchi and Osanai , 1994a; Deguchi et al ., 1996). Moreover, the calcium oscil lations that follow t he initial cortica

fl a s h propa ga t e a s di st i nc t w a v es, r a t her t ha n a s s y nc hro

nous elevat ions (D eguchi and M orisaw a, 1997).

Prophase-arrested oocytes of several bivalve species gen

erate at least one calcium transient a nd/or undergo germi

na l v esi c le b r ea kdown (G VBD ) w hen t r ea t ed w i t h a c t i v a t

ing a gents (D eguchi and Osanai , 1995; Lippai et al ., 1995Fong et a l . , 1997). External calcium infl ux is apparentlinvolved in suc h a ctiva tion s, since (i) G VBD is preceded b

calcium infl ux and prevented by calcium infl ux blocker(D ube a nd G uerrier, 1982; Kada m et al., 1990; Juneja et al

1994; Juneja and Koide, 1996); (ii) calcium ionophore trig

g er s G VB D i n Spisula o o cy t e s i n c u ba t e d i n c a l ci u mc ont a i ni ng s ea wa t er b ut not i n C a FS W (S chuet z , 19 75

Kadam et al ., 1990); and (iii) th e pre-G VBD calcium risinduced by the hormone serotonin often requires externa

calcium to be fully effective (Deguchi and Osanai , 1995)

Similarly, calcium infl ux seems to be involved in optim all

activating metaphase I-arrested oocytes of M y t i l u s, sinc

(D , E) Tw o sets of compressed confocal z series of a C. l acteus oocyt e inject ed w it h t he vit a l ER indica t or DiI , show ing t he forma t ion o

ER microdom ains (arrows) that ma y play a role in producing a norm al calcium response (D , 75 min postrem oval from t he ovary; E, 16

m in postremoval from ov ary). (F)Oocy te from t he starfi sh Pisaster ochraceus,showin g a norm al fertilizat ion-induced calcium w ave (arrow

in t he pres ence of t he ca lcium cha nnel blocker nifedipine. Not e t he conca ve na t ure of t he w a vefront , w hich indica t es a more ra pi

transmission around the periphery than through the center of the oocyte (i.e. , even though the peripheral pathway represents a greate

distance than directly through the center of the oocyte, the calcium wave advances around the cortex of the oocyte before fully traversin

the cent ral ooplasm). (G ) A 3-D cylindrical reconstruction of a t im e-lapse confocal data set show ing fertilization in a Pisasteroocyt e. Fo

such reconstructions, the circular optical sections in a t ime-lapse confocal data set w ere stacked on t op of each ot her so that the vertica

axis equals t im e, and the top of t he rendered cy linder represents t he oocyt e before insemination (Stricker, 1994); vertical scale bar, 200

The r ight -ha nd rect a ngle is t he clea ved cylinder t o depict t he progress ion of t he fert i l iza t ion-induced ca lcium w a ve w it hin t he oocyt

(a rrow ). N ot e t h a t compa red t o t he oocyt e cent er, t he w a ve t ra vels more ra pidly in t he cort ex, judging from t he s ha llow er s lope of t h

w avefront (i.e. , less t im e elapses during simi lar distances t raveled in t he cortex vs center). (AC ) Stricker, unpublished observations; (D , E

Stricker et a l . (1998); (F, G ) Stricker et a l . (1994). Horizontal scale bar, 50 m .

16Fert i l i zat i on-Induced C a2 Signals

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

6/20

5/25/2018 1-s2.0-S0012160699993405-main

7/20

either a rapid replacement of high-potassium seaw ater w ith

CaFSW (Deguchi and Osanai , 1994b) or an incubation in

c a l c ium i nfl ux b l oc ker s b efore t he pot a s s ium t r ea t m ent

(Krantic a nd Riva iller, 1996) signifi cant ly reduces the num -

ber of oocyt es forming polar bodies.

N ev ert hel es s, i nt erna l c a l ci um r el ea s e m a y a l s o oc c ur

during activation of several bivalves examined, given that

(i ) v a ri ous a goni st s c a n t r i gger c a l ci um t r a ns ient s a nd a tleast som e G VBD in C aFSW (G uerrieret al .,1993; G obet etal ., 1995; Lippai et al ., 1995); (ii) IP 3 is capable of el ici t ingG VBD (Bloom et al ., 1988; G uerrier et al ., 1996); and (iii)s er ot oni n, whi c h nor m a l l y i nduc es a t r a ns i ent r i s e i n IP 3levels prior t o G VBD (G obet et a l . , 1994), fails to causeG VBD in heparin-loaded specimens (D eguchi and Osanai ,

1995).

ANNELIDA

Ferti l ization causes metaphase I-arrested oocytes of the

a nnel i da n wor m Chaetopterus to undergo 327 calciumt r a ns i ent s t ha t c ea s e b y 10 min postinsemination (Eck-

berg and Miller, 1995; Fig. 1E). The fi rst calcium tran sient

fa i ls t o propa ga t e c om pl et el y a c ros s t he oopl a s m a nd i s

foll owed b y m ul t i pl e ful ly propa ga t ed c a l ci um w a v es t ha t

eventually arise from a repeated pacemaker si te (Eckberg

and Miller, 1995). Although the sources of calcium mobi-

lized during ferti l ization have not been directly analyzed,

prophase-arrested oocytes of Chaetopterus (Ikegami et al .,

1976) and Pectinaria (Anstrom and Summ ers, 1981) typi-c a l ly r eq ui r e ext er na l c a l c i um t o m a t ur e properl y . S im i -

l a rl y , w h e n t r ea t e d w i t h e xc es s po t a ss iu m , m e t a ph a s e-

arrested Chaetopterus specimens produce calcium w aveslike t hose of fertilizat ion (Eckberg an d M iller, 1995), collec-

t i v ely s ugges t i ng t ha t a c t i v a t i on depends on ext erna l c a l -

cium . How ever, oth er fi ndings implicat e int ernal sources of

c a l c ium , s i nce hi gh c onc ent r a t i ons of c a l c ium i onophor e

a c t i v a t e Chaetopterus oocy t es i n Ca FS W (E ckb er g a ndC arroll, 1982), and t he application of C aM g-free seaw at er by

itself leads to G VBD in Sabel lari a (Peucellier, 1977). More-over, homogenates of Chaetopterus oocytes mobilize cal-cium in response to either IP 3 or the thiol reagent t him ero-

sal (Thomas et a l . , 199 8), w hi c h i n ot her c el ls t ends t osensitize IP 3Rs (Miyazakiet al.,1992a) but m ay a lso releasec a l c i um t hr ough R y R s i n s om e c a s es (M c D ouga l l e t a l . ,

1993).

ECHIURA

Follow ing insemina tion , prophase-arrested oocytes of th e

ec hiur a n w orm U rechis genera t e a c a l ci um t r a ns ient t ha tdoes not form a distinct point-source wave (Stephano and

G ould, 1997). The init ial calciu m tran sient is follow ed by a

plateau of elevated calcium (Fig. 1F) that can culminat e in

pa rt i c ul a rl y hi gh nuc l ea r c a l c i um l ev els , a nd ha l f of t he

fertilized oocytes also exhibit at least one more calcium rise

t ha t pr opa ga t es i n a non-wa v el i ke fa s hi on (S t epha no a nd

G ould , 1997).

The ferti l ization-induced calcium response of U rechiinvolves calcium infl ux, based on (i) 45Ca m ea s ur em ent

(Johnston and Paul, 1977); (i i) al teration of ferti l ization

induced calcium dynamics by perfusions of seawater con

taining t he calcium chelating agent BAPTA (Stephano an

G ould, 1997); and (iii) duplication of the calcium respons

i n t h e a b se nc e o f s pe rm b y o pe n in g o ol em m a l c a lc iu m

chan nels (Stephano and G ould, 1997). Accordingly, treat inunferti l ized oocytes w ith exogenous trypsin (Johnston an

Paul, 1977) or t he P23 peptide from sperm acrosome

(Stephano and G ould, 1997) elici ts ferti l ization-like cal

c i um dy na m i c s a nd/or a c t i v a t i on, pr ov i ded t ha t ext erna

c a l ci um i nfl ux i s a l l ow ed t o oc c ur (S t epha no a nd G oul d

1997). Unferti l ized oocytes can also mobilize internal cal

cium stores in response to IP 3, b ut s uc h t r ea t m ent s do no

fully mimic the ferti l ization response or trigger activatio

(Stephano and G ould, 1997). C ollectively, such dat a reveal

need for ext erna l c a l ci um i nfl ux duri ng fer t i li za t i on, a l

though a supplementat ion by int ernal calcium release can

not be ruled out (Stephano and G ould, 1997).

ARTHROPODA

In the shrimp Sicyoni a (Phylum Arthropoda, SubphylumCrustacea), magnesium ions in the seawater activate meta

phase I-arrested oocytes by ca using an in tracellular calciu m

wave in these specimens (Lindsay et al ., 1992). A similac a l ci um w a v e i s i nduc ed b y eit her M g 2 in the absence o

external calcium or calcium ionophore treatments in Mg

FSW (Lindsay et a l . , 1992). Moreover, the Mg 2-induceC a 2 w a v e i s m i m i c k e d b y I P 3 injections and blocked b

tyrosine kinase inhibitors, suggesting the involvement oa n I P 3-dependent release of internal calcium stores regu

lat ed by a ty rosine kinase-based signaling path w ay (Lindsa

and Clark, 1994). In the presence of sperm, activated oo

cytes invariably generate a second calcium t ransient w hic

ma y represent a ferti l ization-induced calcium response

although this rem ains t o be verifi ed (Lindsay et al ., 1992)Magnesium ions also activate unferti l ized oocytes of th

pr a wn Palaemon b y t r i gger ing a s er ies of IP 3-mediatecalcium oscil lations that last for 76 5.5 min, follow ed b

a 49.6 4.5-m in postoscillat ory plateau of elevat ed calcium

t h a t r el i es o n e x t er n a l c a l ci u m i n fl u x (G o u d ea u a n

G oudeau, 1996, 1998). Whether any of these calcium tran

sients propagate as waves has not been established. More

over, as in Sicyoni a,the t ype of calcium response normallelici ted by ferti l ization rema ins unclear.

ECHINODERMATA

E chi noi dea

During ferti l ization, eggs of sea urchins and other echi

noids (Phy lum Echinodermat a, C lass Echinoidea)generate

single 5 - t o 1 0 -m i n c a l c i um t r a ns i ent t ha t s pr ea ds a s

w ave across th e ooplasm (Steinha rdt et al., 1977; G illot an

Whitaker, 1993; Table 1). In Lyt echinus, the ferti l ization

16Fert i l i zat i on-Induced C a2 Signals

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

8/20

induced calcium w ave is directly preceded by an infl ux of

calcium leading to a cortical fl ash t hat is not required for

normal wave production (McDougall et al., 1993; Shen andBuck, 1993). The calcium wave is then followed by a few

p o st f e r t i l iz a t i o n c a l c i u m t r a n s i e n t s (S t e i n h a r d t , 1 99 0;

Br owne et al ., 1996; Fig. 1G ).Although external calcium infl ux occurs at the onset of

sea urchin ferti l ization (Paul and Johnston, 1978), normalferti l izations can sti l l be achieved in CaFSW using prere-

acted sperm (Schmidt et al., 1982; McDougall et al., 1993).Accordingly, unferti l ized sea urchin eggs are activated by

calcium ionophore in CaFSW (Steinhardt and Epel, 1974)

but not by excess potassium in calcium-containing seawa-

ter (Schmidt et al., 1982), suggesting t hat calcium infl ux isnot a major driving force in activation. Conversely, ferti l i-

za t i on c a n b e i nhi b i t ed b y pr et r ea t m ent s wi t h l a nt ha num

or calcium chelators to block calcium infl ux (C reton and

Jaffe, 1995), indicating that calcium infl ux may indeed play

a necessary role (for a discussion of the discrepancies, see

Jaffe, 1990; C reton and Jaffe, 1995; Jones et al ., 1998b).As point ed out in previous review s (Whit aker and Sw ann ,

1993; Shen, 1995), unfertilized sea urchin eggs can release

internal calcium stores via IP 3- or non-IP 3-mediated mecha-

ni s m s . Fol low i ng i ns em i na t i on, a c a l ci um w a v e oc c urs i n

the presence of inhibitors against IP 3R s or R y R s b ut not

w hen both inhibitor types are used, suggesting that t he tw o

receptors funct ion redundant ly during fertiliz at ion (G alione

et al., 1993; Lee et al., 1993). H ow ever, it w as no t reportedif the specimens displaying calcium waves underwent nor-

mal cleavage, and other analyses indicate that ferti l ization

m a y a c t ua l l y r eq uir e IP 3-mediated calcium release (Mohri

et al., 1995; Lee et al., 1996; Lee and Shen, 1998; Carroll et

al ., 1999), which in turn depends on functional phospho-lipase C (PLC ) (Carroll et a l . , 1999). Thus, i t rem ainsunc l ea r i f s ea ur chi n R y R s c a n ful ly s ubs t i t ut e for IP 3R s

during normal development.

A st er oi dea

Prophase-arrested oocyt es of sta rfi sh (Ph ylum Echinoder-

m ata, C lass Asteroidea) undergo G VBD in response to the

hor m one 1 -m et hy l a deni ne a nd proc eed t hr ough m ei osi s

w ith out arrest (Meijer and G uerrier, 1984). D uring fertili-

z a t i on i n Pisaster a n d o t h er s t a rfi s h , m a t u r in g o o cy t e sproduce a single w avelike calcium transient t hat m aintain s

elevated [Ca 2]i for 1030 min (Eisen and Reynolds, 1984;

Strickeret al., 1994). The w ave m ay (C arrollet al., 1997) ormay not (Strickeret al .,1994) follow a distin ct cort ical fl ashand is generally com pleted about an hou r before th e onset of

some postfertilization calcium oscillations (Stricker, 1995;

Fig. 1H).

External calcium infl ux does not appear to be required for

t he produc t ion of a c a l ci um w a v e, s i nc e unfer t i li zed oo-

c y t es c a n b e a c t i v a t ed b y c a lc iu m i on o ph o re i n C a F SW

(Steinhardt et a l ., 1 97 4), a nd a nor m a l -a ppea ri ng w a v econtinues to be generated w hen oocytes are ferti l ized in the

p re se n c e o f t h e c a l c iu m c h a n n e l b l oc k er n i f ed i pi n e

(Stricker et al ., 1994) (Fig. 2F). As further evidence for in-

ternal calcium release, unferti l ized oocytes are capable o

generating calcium transients in response to either IP 3 o

agents such as ryanodine, caffeine, and cyclic ADP-ribos

(cADPr)that target RyRs (Stricker, 1995; Santella, 1996). In

prophase-arrested specimens of A ster ina pect in i fera, botIP 3- and non-IP 3-mediated calcium release can yield a cal

c i um fl ux i n t he c y t opla s m a nd n uc l eus , a nd t he n uc l ea

calcium elevation in particular appears to play an importanrole in G VBD , based on injections of agonists or BAPTA

(Sant ella an d Ky ozuka , 1994, 1997). H ow ever, during fertil

izations of post-G VBD specimens in other starfi sh species

c a lc i um s ee m s t o b e m o b i li z ed p re do m i n a n t l y t h r ou g

IP 3R s, giv en t ha t (i ) pr et r ea t m ent w i t h hepa r in i nhi bi t

cleavage and causes aberrant calcium dynam ics (Stricker

1 99 5); a nd (i i ) fer t i li za t i on-i nduc ed c a l c i um w a v es a n

c l ea v a ge a r e eli m i na t ed b y preinjec t ions of r ec om b i na n

src-homology 2 (SH2) domains of PLC , w h i c h b l o c k I P 3m edi a t ed c a l c i um r el ea se r egula t ed b y t y r os ine ki na s e

(Carroll et al ., 1997).

CHORDATA

U r o c h o r d a t a

During ferti l ization, metaphase I-arrested oocytes of as

cidians (Phylum Chordata, Subphylum Urochordata, Clas

A sc i di a c ea ) genera t e m ul t i ple c a l ci um w a v es w hi l e c om

pleting meiosis (Speksnijder e t a l . , 1989; McDougall anSardet, 1995; Sardet et al ., 1998; Fig. 1I). In Phal lusia a nother species, t he fi rst ferti l ization-induced calcium tran

sient, or activat ion w ave (Speksnijder, 1990a), originat e

f ro m t h e po in t o f s pe rm e nt r y a n d d i re ct l y pr ec ed es

microfi lament -m ediated cortical contraction (Speksnijdeet al ., 1990a,b,c; McDougall and Sardet, 1995; Roegiers eal ., 1996). Subsequently, each ferti l ized oocyte produceabout one to tw o dozen calcium w aves that shift their onse

s i t e t ow a r d t he v eget a l pol e, w here t hey ev ent ua l l y ori gi

nat e from an ER-rich vegetal pacemaker w hile displaying

m ore cortica lly enha nced propagation (Speksnijder, 1992

McDougall and Sardet, 1995).

Ferti l izations of Phal lusia ooc y t es i n Ca F S W c a n y i elnormal calcium dynamics and development (Speksnijder eal ., 1989). Accordingly, ionophore treatments of unferti lized oocytes in CaFSW elicit cortical contractions and pola

body formation (McDougall et al .,

1995), suggesting tha

the calcium mobilized during ferti l ization comes from in

t er na l s t or es . Howev er , i n ot her s t udi es of Phal lusia, remova l of external calcium causes aberrant ferti l ization po

tentials an d increased polyspermy, w hich can be prevente

b y a puls e of nor m a l s ea wa t er a t t he ons et of fer t i li za t i o

(G oudeau and G oudeau, 1993). Simila rly, C i o n a oocytefer t i l ized i n C a FS W fa i l t o produc e ei t her t he l a t er-oc

c urr ing c a l c ium os ci l la t i ons of nor m a l fer t i li za t i ons or

second polar body (Sensui an d M orisaw a, 1996), collectivel

suggesting that development requires an infl ux of calcium

A n IP 3-m edi a t ed pa t hwa y i s a ppa r ent l y ut i l i zed dur i n

f er t il iz a t i on , g iv en t h a t h e pa ri n o r a n a n t i bo d y a ga i n s

IP 3Rs disrupts fertilization-induced calcium oscillations in

164 Stephen A . Str ick e

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

9/20

Ciona, w h erea s ru t h en i um red , w h i ch c an b e u s ed t oi nhi b i t R y R s r a t her t ha n IP 3Rs, has no noticeable effect

(Russo et al ., 1996; Yoshida et al ., 1998). Simila rly, unfer-ti l ized oocytes of C i o n a or Phal lusia generate ferti l ization-like calcium oscil lations and form polar bodies when sub-

jec t ed t o ( i ) a denophos t i n, a pot ent a goni s t of IP 3Rs; (ii)

continuously perfused IP 3; or (iii) multiple IP 3 pulses (Mc-

Dougall and Sardet, 1995; Albrieux et al., 1998; Yoshida etal ., 1998). C onversely, treatm ents w ith ryanodine, cADP r,caffeine, or nicotinic acidadenine dinucleotide phosphate

(N A A D P ) t o s t i m ul a t e non-IP 3-b a s ed s i gna l i ng pa t hwa y s

fail to trigger a m arked calcium response or full activation

(McDougall and Sardet, 1995; Albrieux et al ., 1997, 1998;Wilding et al ., 1998).

However, contributions from non-IP 3-mediated calcium

release cannot be ruled out for C i o n a or Phal lusia, giventha t (i) heparin-loaded oocytes display on e to a few calcium

t r a ns ient s a f t er fer t i li za t i on or s perm ext ra c t i nject i ons

(Russo et a l . , 1996; Wilding and D ale, 1998); and (i i) as i gna l i ng pa t hw a y t r i gger ed b y ni t r ic oxide c a n c a us e a

c a l c ium fl ux a ppa r ent l y v i a r ec ept ors ot her t ha n IP 3R s

(G rumet to et a l . , 1997; Wildin g et a l . , 1998). Mo reover,non-IP 3 receptors may cont ribute to highly localized an d/or

ephem era l c a l c i um t r a ns ient s , w hi c h a r e not ea si l y de-

tected but are nevertheless needed for regulating oolemmal

capacitance and currents (Albrieux et al., 1997, 1998; Wild-in g et al ., 1998).

CALCIUM WAVES DURINGFERTILIZATION IN DEUTEROSTOMESAND PROTOSTOMES

L. F. Jaffe (1983, 1985) hypothesized that deuterostome

animals release internal stores of calcium to generate cal-

c iu m w a v es d u ri n g f er t il iz a t i on , w h e re as t h e f er t il iz e d

ooc y t es of prot os t om es ut i l i ze ext erna l c a l c ium i nfl ux t o

produc e non-w a v el i ke c a l c i um t r a ns i ent s . How ev er , a s

s um m a r i zed i n Ta b l e 1 , poi nt -s ourc e c a l ci um w a v es oc -

cur not only in deuterostomes but also during ferti l ization

(Eckberg and Miller, 1995; Stricker, 1996b; D eguchi and

Morisaw a, 1997) or oocyte activat ion (Lindsay et al., 1992)i n s ev era l phy l a t ha t a r e gener a ll y b el i ev ed t o r epresent

protostom e l ineages, based on both classical em bryological

criteria [Pearse e t a l . ,

1987; G ilbert, 1994althou gh see

Hertzler an d C lark (1992) for a n al ternative interpretat ion

of Sicyonias ontogeny] and molecular-based phylogenies(Aguinaldo and Lake, 1998; Winnepenninckx et al ., 1998).E ven i n m a m m a l s w here s om e s y nc hronousl y propa ga t ed

calcium fl uxes can occur during maturation or late ferti l i-

zation (Carroll et al., 1994; Shiraish i et al .,1995), the initialfertilizat ion-induced calcium tran sients are w avelike (Fuji-

w a r a et a l . , 1993; Wu et a l . , 1996), and currently onlyec hi ur a n pr ot os t om es ha v e b een s hown t o l a c k c a l c i um

w aves (Stephano and G ould, 1997).

The m ea n v el oci t i es of fert i l i za t i on-i nduc ed c a l c i um

w a v es f a l l w i t h i n a r el a t i ve ly n a rr ow r an g e o f 1030

m/s, w hich is consistent w ith a fundam entally conserved

reaction-diffusion-based m echanism of w ave propagatio

(Jaffe, 1991, 1995). As diffusible messengers for propagatin

such global calcium w aves, oocyt es may use IP 3 (Allbritto

et a l . , 1992) o r c a l c iu m i o n s t h a t p ro m o t e a c a l ci u minduced calcium release (C ICR) acting on RyRs (G al ion

and Sum m erhill, 1996) and/or IP 3Rs (G alione et al ., 1993Whitaker and Swann, 1993). In some species (Mohri an

Ha m aguchi, 1991; Strickeret al .,1994; Font anilla a nd N uccitell i , 1998), the calcium wave travels faster around th

cortex than through the central ooplasm and thus display

a concav e w avefront (Figs. 2F and 2G ). Such differences in

transmission rates may be due to an enhanced distributio

of peripheral ER structures (McPherson et al ., 1992; Mehm a n n et al., 1995; Stricker et al., 1998; Fissore et al., 1999an d/or a gradient of IP 3concen trat ions (Wagneret al .,1998

SINGLE VS MULTIPLE CALCIUMTRANSIENTS FOLLOWINGFERTILIZATION

Ferti l ization in most animals, including numerous mam

m a l s e xa m i n ed , r es u lt s i n m u l t i pl e c a lc iu m t r a ns ie nt

(Ta b l e 1). S uch os ci l la t or y c ha nges i n free c a l ci um a r

generally believed to arise from interactions between tw

separate pools of bound c alcium (Berridge, 1991)or from th

b iph a s ic r el ea s e o f c a lc iu m w i t h in a s in gl e p o ol t h a t i

d if fe re nt i a ll y r eg ul a t ed b y s u ch m o d u la t o rs a s I P 3 a n

calcium (De Young and Keizer, 1992).

The common occurrence of fertilization-induced calcium

os ci l la t i ons m a y s i m ply r efl ect t he need for a l ong-t erm

calcium response without the continuous elevation of cal

cium tha t ca n be toxic t o cells (D ow d, 1995). On the ot hehand, an oscil latory response could provide an inherentl

m ore robust t rigger of cellular processes, since it ca rries no

only the amplitude-related signal that accompanies a soli

tary calcium pulse but also frequency-encoded informa

tion (G u and Spitzer, 1995; Tang and Othmer, 1995). Ac

cordingly, m am m als can display species-specifi c difference

i n t he freq uenc i es of t hei r fer t i li za t i on-i nduced c a l ci um

oscillation s (Wu et a l . , 1997; Jones, 1998), and a singlc a l ci um puls e oft en fa i ls t o a c t i v a t e a ni m a l ooc y t es ful l y

w hereas m ultiple calcium t ransients successfully releas

o o cy t e s f ro m m e i ot i c a rr es t t o f or m b ot h p ol a r b o d ie

(D eguchi and Osan i, 1995; Stricker, 1996b; Albrieux 1997

Lawrence et al ., 1998; Ozil, 1998).The q uest i on t hen a r is es : w hy do c ni da r ia ns , ec hi no

derm s, fi sh, and frogs generate a soli tary calcium transien

at fertili za ti on (Figs. 1A, 1G , 1H, 1J, and 1K)? In cases w her

meiosis either fully precedes ferti l ization (sea urchins an

cnidarians) or lacks a natural arrest point once G VBD ha

been triggered (starfi sh), a soli tary ferti l ization-induce

transient may be suffi cient, given that a resumption from

m ei ot i c a r r es t i s not r eq ui red. A l t er na t i v el y , unl i ke t h

m a ny hour s t ha t el a ps e b et ween m ei ot i c r es um pt i on a n

interphase in m am ma lian zygotes (Jones, 1998; Fig. 1L

fer t i li za t i on i n fi s h (Iwa m a t s u a nd Oht a , 19 78) a nd frog

(Rugh, 1951) can trigger a rapid (1030 min) transitio

16Fert i l i zat i on-Induced C a2 Signals

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

10/20

from MII arrest to pronuclear formation prior to fi rst cleav-

age. Accordingly, the abbreviated nature of the postferti l-

ization phase in these zygotes could obviate the need for a

repeated series of calcium transients such as found in mam-

mals (Jones, 1998).

EXTERNAL CALCIUM INFLUX VSINTERNAL CALCIUM RELEASE DURINGFERTILIZATION

The current database suggests that a fertilization-induced

infl ux of external calcium is not restricted to protostomes

as postulat ed by Jaffe (1983, 1985) but fun ction s along w ith

i nt er na l c a l c i um r el ea s e t hr oughout t he a ni m a l ki ngdom

(Table 2). Even in mammalian oocytes that can be activated

by an ionophore-induced release of internal st ores w ithout

external calcium being present (Steinhardt et a l . , 1974),ferti l ization apparently requires an infl ux of external cal-

cium to refi l l internal stores an d t hereby al low prolonged

calcium oscillations to occur (Igusa a nd Miyaz aki, 1983;Kline an d Kline, 1992b; Miy aza ki, 1995; McG uinness et al .,

1 996 ). S uch i nfl ux s eem s t o ut i l i ze a c a pa c i t a t i v e or

store-operat ed form of calcium entry (Pa rkeh and Pen ner,

1 997 ) t ha t i n t ur n depends on t he deplet i on of i nt erna l

calcium stores an d either positive or negative feedback on

the store-operated plasmalemmal channels by such diffus-

ible m essengers as calcium (Barritt, 1998), in ositol 1,3,4,5-

tet rakisphosphat e (IP 4) (Bird and P ut ney, 1996), an d calcium

infl ux fa ctor (C IF) (C sutora et al ., 1999).O n t h e o t h er h a n d, i t i s c l ea r t h a t o oc y t es c a n a ls o

m obilize int ernal calcium stores, and such int ernal release

typically involves an IP 3-m edi a t ed s i gna l i ng pa t hw a y t ha tb ec om es s ens i t i zed a s t he ooc y t e m a t ur es (Chi b a et a l . ,1990; Mehlman and Kline, 1994; Abbott et al., 1999). Bothprotostom e and deuterostome oocyt es have the capacity for

IP 3-based calcium signaling, and in several animal groups

IP 3-m edi a t ed c a l ci um r el ea s e a ppea rs t o b e r eq ui red for

nor m a l fer t i li za t i on (Ta b l e 2 ). C onv er sely , t he a b i li t y t o

produce global calcium transients via either RyRs or other

non-IP 3 ty pes of calcium release channels (Willmot et al .,1997) has been demonstrated for only a few taxa (Table 2).

Accordingly, the presence or absence of functional RyRs in

m a m m a l i a n ooc y t es v a r i es a m ong s pec i es or ev en wi t hi n

different strains, in the case of m ice (Jones et al .,

1995b).

R ega r dl es s of w het her ext erna l or i nt erna l s ourc es of

calcium are uti l ized during ferti l ization, the calcium tran-

sients generated by such mechanism s can facil i tat e various

im portant processes ranging from polysperm y prevent ion to

m eiotic resumption. This facil i tation presumably occurs

via direct or indirect effects of calcium transients on dow n-

stream effectors such as calciumca lmodulin-dependent

k i n a s e s (C a M K s ), c y t o s t a t i c f a c t o r (C S F), m a t u r a t i o n -

promoting factor (MPF), mitogen-activated protein kinase

(MAP K), an d protein kin ase C (PKC ) (G allican o et al.,1993;Whitaker, 1995, 1996; Sagata, 1996; Raz and Shalgi, 1998).

In particular, the activity of type II C aMK can be modulated

by oscil latory calcium transients (De Koninck and Schul-

m an, 1998) and is generally believed to be essential for cel

cycle progression (Baitin ger et al., 1990; Lorca et al ., 1993D uPont , 1998; Johnson et al ., 1998).

RECEPTOR-MEDIATED VS SPERM-FACTOR-BASED SIGNALING PATHWAYS

Essential ly two groups of opposing, but not necessaril

m ut ua l l y excl usi v e, hy pot hes es ha v e b een propos ed t

account for the upstream pathways by which sperm trigge

calcium transients during ferti l ization (D ale and D eFelice

1990) (Fig. 3). In receptor-m ediat ed hy poth eses (Jaffe, 1990

Foltz and Shil l ing, 1993), t he sperm is view ed as an hon

orary horm one (Whit aker and C rossley, 1990) th at gener

a t es t he c a l ci um r is e from t he out s i de-i n b y b i ndi ng t

oolemmal surface receptors. Conversely, sperm-factor hy

potheses postulate tha t following gam ete fusion, the sperm

introduces internally a cting m olecule(s)int o th e ooplasm t

trigger th e ca lcium response (Sw ann , 1990, 1993).

Receptor-m ediated hy potheses are consisten t w ith (i) thi dent i fi c a t i on of func t i ona l s perm l i ga nds a nd oolem m a

receptors in various species (Myles, 1993; Foltz, 1995

Ohlendieck and Lennarz, 1995); (ii) the demonstration tha

unferti l ized oocytes are capable of el ici t ing calcium tran

sients via signaling cascades involving int egrins, G -proteins

a n d /o r t y r os in e k i n as es , w h i ch i n m a n y c el l t y p es a r

stimulated by receptor activation (Miyazaki, 1988; Moor

et al ., 1993; Shilling et al ., 1994); and (iii) the perturbatioof norm a l fer t i li za t i on-i nduced c a l c ium dy na m i c s foll ow

ing th e inhibition of G -proteins or t yrosine kinases that i

t u r n m a y f u n ct i o n d o w n s t re a m o f r ec ep t or a c t i va t i o

(Mi ya za ki, 1988; Fissore and Ro bl, 1994; G lah n et al.,1998For more direct support of a receptor-mediated pathway

ext erna l a ppl i c a t i ons of s perm -deri v ed c om ponent s c a

elicit a calcium transient in oocytes or zygotes of severa

species (Osaw a et a l . , 1994; Stephano and G ould, 1997Shilling e t a l . , 1 9 9 8 ). Howev er , i n m a m m a l s t her e i s nconcrete evidence for similar externally acting sperm mol

ec ul es t ha t c a n t r i gger c a l c i um t r a ns ient s v i a r ec ept or

m ediated pat hw ays (Evans an d Kopf, 1998). Moreover, nei

ther heterotrimeric G -proteins (Williams et al ., 1998) not y r os i ne ki na s es t a r get i ng S H2 dom a i ns on P LC (Meh

m a n net al.,1998) appear to be required for the fertilizat ioninduced calcium response of mammals, al though i t is pos

sible that other receptor-mediated means of increasing PLC

a c t i v i t y c oul d s t i l l pl a y a r ol e (M ehl m a nn et a l . , 1998Thus, al th ough sperm receptors and dow nstream signalin

pathways are present prior to ferti l ization, i t remains pos

sible that in some animals sperm-receptor binding is no

specifi cally required for generating a normal calcium re

sponse.

Alternatively, sperm-factor hypotheses gain indirect sup

por t fr om t he l a t ent peri od t ha t oc c ur s b et w een s perm

oolemma l contact and calcium transient onset (Whitakereal ., 1989). In mammals, for example, sperm fuse with thegg duri ng t hi s l a t ent per iod s ev era l m i nut es b efore t h

c a l ci um w a v e s t a r t s (La wr enc e e t a l . , 1997; Jones et a l

166 Stephen A . Str ick e

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

11/20

1998b), w hich is consistent w ith t he tim ing required for th e

diffusion of a soluble sperm-supplied molecule, al though

not exclusive proof for such a mechanism (Evans and Kopf,

1998). M o re d ir ec t e vi de n ce c om e s f ro m t h e f a ct t h a t

intracellular injections of soluble sperm extracts can both

generate a ferti l ization-like calcium response in m am ma ls,

ascidians, an d nemerteans (Stricker, 1997; Kyozuka et al .,

1998; Sw ann et al ., 1998; Sakurai et al ., 1999) and triggera c t i va t i o n t h a t c u lm i n a t e s i n po l ar b o dy f or m a t i on

(Stricker, 1997; Wildinget al .,1997)o r even c leav age (Wuetal ., 1997; Fissore et al ., 1998). Furthermore, the fact thatintracytoplasmic sperm injections (ICSI)into the interior of

oocytes produce calcium oscillations (Na kano et al ., 1996)and healthy offspring (Palermo et al ., 1996) demonstratest ha t i nt er a c t i ons b et ween s per m a nd ool em m a l r ec ept or s

are not strictly required for norma l ferti l izat ion.

Such internally a ctin g activat ors w ere once believed to be

small molecules like calcium (Jaffe, 1991) or IP 3 (Tosti etal ., 1993) th at w ere derived directly from th e sperm and/ori n t he c a s e of c a l c i um i ons funneled t hr ough t he s perm

from t he ext ra c el l ula r m edi um i n a c onduit -l i ke fa s hion

(Creton and Jaffe, 1995). Accordingly, calcium injections are

capable of causing a ferti l ization-like calcium w ave in fi s

oocytes (Yoshimoto et al.,1986). H ow ever, neither calciu mn o r I P 3 c a n ful ly m i m i c t he s perm -i nduced c a l c i um r e

s po n se o f m a m m a l s (S w a n n a n d O z i l, 1994), a n d m o r

recent dat a suggest t hat sperm factors are actually protein

aceous in nat ure (Sw ann , 1996; Stricker, 1997; Wu et al1998; Perry et al ., 1999).

A 33-kD a oscillin protein w as originally proposed as

possible oscillogen in mammalian sperm (Parrington et al1996). How ever, subsequent ana lyses have ruled out oscil

l i n a s a c a l ci um -m ob i l izi ng a gent (S wa nn et a l ., 1998Wolosker et al., 1998; Wu et al., 1998; Wolny et al., 1999Thus , a l t erna t i v e a c t i v a t or s s uc h a s a t r unc a t ed form o

c-kit (Sette et a l . , 1997), a perinuclear consti tuent l ikcalicin (Kimura et al ., 1998), or P LC (D upont et al ., 1996Jones et al ., 1998a; Mehlmann et al ., 1998) should be considered, especially i f such sperm-borne oocyt e activat io

fact ors (SOAFs) can be show n to generate a fertilizat ion-lik

calcium response. In a ny case, i t remains t o be determin e

if t he putat ive soluble activat or derived from sperm (i) ex

i s t s a t hi gh enough c onc ent r a t i ons t o b e phy s i ol ogi c a ll

relevant (Evans and Kopf, 1998); (i i) represents a singl

FIG. 3. D iagram of som e possible components of fertilization-induced calcium signaling, show ing receptor-m ediated and sperm-facto

ba s ed pa t hw a ys a s w ell a s cont ribut ions from int erna l ca lcium relea se a nd ext erna l ca lcium infl ux. N ot a l l cellula r s t ruct ures a n

m olecules involved in th e fertilization-induced calcium response are depicted, nor does the diagram n ecessarily fi t th e data obtained from

som e species (e.g.,U rechis). Whether calcium is released from a single or mult iple stores w ithin the oocy te/egg has not been establishe

for a l l a nima ls . Simila rly, i t rema ins t o be det ermined if a n increa s e in P L C a ct ivit y modula t ed by t yros ine kina ses or ot her regula t or

necessarily requires receptor stimulation or if it may also occur in response to soluble sperm factors. Moreover, receptor-mediated an

sperm-factor-based pathw ays need not represent m utually exclusive alternativ es, but instead th ese tw o signaling pathw ays could functio

in concert during fertilization . cADP r, cyclic AD P-ribose; C aMKII, multifunct ional calcium /calm odulin-dependent kina se, type II ; cG MP

cyclic guanosine m onophosphat e; CIF, calcium infl ux factor; ER, endoplasmic reticulum ; IP 3, inositol 1,4,5-trisphosphate; IP 3Rs, inosito

1,4,5-trisphosphate calcium channel receptors; IP 4, inos it ol 1,3,4,5-t et ra kisphospha t e; NA A DP , nicot inic a cida denine dinucleot id

phosphate; NAADPR, nicotinic acidadenine dinucleotide phosphate calcium channel receptor; PLC, phospholipase C; RyRs, ryanodin

calcium channel receptors.

16Fert i l i zat i on-Induced C a2 Signals

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

12/20

(Sw ann et al., 1998) or mult iple molecule(s) w ithin any onesperm (Wilding and Dale, 1998; Perry et al ., 1999); (iii) isw ell conserved a cross phyla (Wilding a nd D ale, 1997); (iv)

directly affects IP 3 levels (Jones et al ., 1998a) or alters IP 3Rfunc t i oni ng b y a l t er na t i v e m ec ha ni s m s (G a l i one et a l .,

1997); a nd (v) acts in isolation of (Sw ann et al., 1998), or inc onjunc t i on w i t h, r ec ept or -m edi a t ed pa t hw a y s (Tesa r i k,

1998) (Fig. 3).

FUTURE DIRECTIONS

The current dat abase indicates that both protostomes and

deuterostomes exhibit ferti l ization-induced calcium w aves,

IP 3-m e d ia t e d c a lc iu m s ig na l in g, a n d t h e a b il it y t o u s e

int ernal and/or external sources of calcium during fertiliza-

tion. Such fi ndings fail to support a clear-cut distinction in

c a lc iu m s ig n al in g m o d es f or t h e se t w o m a jo r g r ou ps o f

a n i m a l s a n d i n st e a d s ug ge st t h a t f u nd a m e n t a ll y s im i l a r

pa t t erns of fer t i li za t i on-i nduced c a l ci um s i gna l i ng exi s t

throughout the animal kingdom, as has been concluded byThomas e t a l . (1998). How ever, in spite of such generaltrends, specifi c mechanisms of modulating calcium levels

d u ri n g f er t il iz a t i on m a y t u rn o u t t o v a ry s ig ni fi c a n t ly

w ith in certain species th at eit her have been exam ined [e.g.,

U rechi s (S t epha no a nd G oul d, 1 997 )] or ha v e y et t o b ea n a l y ze d. Th u s, f or a m o r e c om p l et e u n d er st a n d in g o f

ferti l ization-induced calcium signaling, additional analyses

a r e needed, pa rt i c ul a rl y a m ong nonm a m m a l i a n s pec ies

w hi c h c a n di ffer fr om m a m m a l s w i t h r ega rd t o (i ) m ei ot i c

arrest points reached before fertilization; (ii) orientation of

t h e s pe rm t o t h e o o le m m a ; (i ii ) t y p es o f e xt r a ce ll u la r

investment s around the oocyt e; and (iv) internal vs externalmodes of insemination. These supplemental studies should

ext end b ey ond fer t i li za t i on b ot h t o ensur e t ha t develop-

ment proceeds normally (Stricker and Whitaker, 1999) and

to determine i f there are ontogenetic changes in either the

s pa t i ot em por a l pa t t er ns of t he c a l ci um r es pons e or t he

embryos sensitivities to various calcium-releasing agonists

(Sousa et al ., 1996a; Stricker, 1996a). In addition, furthera na l y s es c om b i ni ng c a l c i um -i m a gi ng m et hods wi t h el ec -

trophysiological techniques such as previously performed

on several animal groups (Miyazaki et al.,1986; McD ougallet a l . , 1993; Stephano and G ould, 1997) should help toelucidate various regulatory m echanisms, particularly w ith

respect to the modes an d roles of external calcium infl ux

during ferti l ization.

Although in some species supplemental signals such as

pH c ha nges m a y b e r eq ui r ed i n a ddi t i on t o c a l c i um t r a n-

sients (G ould a nd St ephano, 1989), an int racellular calcium

fl ux nev er t heless r em a i ns a n ess ent i a l c om ponent of t he

ferti l ization response in al l animals examined. Combined

w i t h c ont i nuing i nv est i ga t i ons i nt o t he ups t rea m m odul a -

t or s a nd downs t r ea m t a r get s of fer t i li za t i on-i nduced c a l -

c i um t r a ns ient s , furt her s t udi es s uc h a s out l i ned i n t hi s

review should eventually provide an integrated view of how

calcium signals allow fertilized oocytes and eggs to develop

nor m a l l y .

ACKNOWLEDGMENTS

D rs. R . Cret on, R . D eguchi, R . Fis sore, M . G ould, K. J ones , C

L a mbert , L . L inds a y, A . M cDouga ll , S. Shen, C. Simerly, a nd K

Sw ann provided extremely h elpful feedback but are neither respon

sible for inaccuracies nor necessarily in agreement with the view

t ha t a re expres s ed in t his review . St udies on Micrura a laskens

w ere conduct ed a t Frida y Ha rbor L a bora t ories , us ing la bora t or

space generously provided by t he director, Dr. A. O. D . Willow s.

REFERENCES

Abbott , A. L., Fissore, R. A., and D ucibell a, T. (1999). Incom petenc

of preovulatory mouse oocytes to undergo cortical granule exo

cyt os is follow ing induced ca lcium os cil la t ions . D ev . B i o l . 207

3848.

Abdelmajid, H., Leclerc-David, C. , Moreau, M., G uerrier, P. , an

Ryaz anov, A. (1993). Release from met aphase I block in inverte

b r at e o o c y t e s: P o s si b l e i n v o l v em e n t o f C a 2/c a l m o d u l i n

dependent kinase III. In t . J. D ev. B io l . 37, 279290.

A bra ha m, V. C. , G upt a , S. , a nd Fluck, R . A . (1993). Oopla smis egrega t ion in t he m eda ka (Oryzias lat ipes ) egg. B i o l . B u l l . 184

115124.

A guina ldo, A . M . A ., a nd L a ke, J. A . (1998). Evolut ion of t h

mult icellula r a nima ls . A m . Z o ol . 38, 878887.

Albrieux, M., Lee, H. C ., and Villaz, M . (1998). C alcium signalin

by cyclic A D P -ribos e, N A AD P , a nd inos it ol t r is phos pha t e i

involved in distinct functions in ascidian oocytes. J. Biol. C hem

272, 1456614574.

Albrieux, M ., Sardet, C . , and Villaz, M. (1997). The tw o in tracellu

l a r C a 2 release chan nels, ryanodine receptor and inositol 1,4,5

trisphosphate receptor, play different roles during fertilization i

ascidians. Dev. B io l . 189, 174185.

A ll b ri t t o n , N . L ., M e y er , T. , a n d S t ry e r, L . (19 92 ). R a n ge o

messenger action of calcium ion and inositol 1,4,5-trisphosphate

Science258, 18121815.

Allen, R. D . (1953). Fertilizat ion a nd a rtifi cial activa tion in t he eg

of the surf-clam, Spisula sol id i ssim a. B io l . Bul l . 105, 213239.

Anstrom, J ., and Summ ers, R . G . (1981). The role of extracellula

C a 2 in t he a ct iva t ion of Pectinariaoocytes.Dev. Grow th. Di f fe

23, 415420.

Arnoult , C . , Albrieux, M., Antoine, A. F. , G runw ald, D ., Marty , I

a nd V illa z , M . (1997). A rya nodine s ensit ive ca lcium s t ore i

ascidian eggs monitored by whole-cell patch clamp recordings

C e l l C a l c i u m 21, 93101.

A ust in, C. R . (1965). Fert i l iza t ion. P rent ice H a ll , Englew oo

C lif fs , N J.

Ayabe, T., Kopf, G . S. , and Schultz, R. M . (1995). R egulation omou se egg activa tion: P resence of ryanodine receptors and effect

of microinjected ryanodine and cyclic ADP ribose on uninsemi

na t ed a nd ins emina t ed eggs .D evelopm ent 121, 22332244.

B a it inger , C. , A ldert on, J . , P oenie, M . , Schulma n, H. , a nd St ein

hardt, R. A. (1990). M ultifunct ional C a 2/calm odulin -dependen

prot ein kina s e is neces s a ry for nuclea r envelope brea kdow n

J. Cell Biol. 111, 17631773.

B a rrit t , G . J. (1998). D oes a decrea s e in s ubpla s ma lemm a l C a 2

expla in how s t ore-opera t ed C a 2 cha nnels a re opened? Ce

C a l c i u m 23, 6575.

BenYosef, D., and Shalgi, R. (1998). Early ionic events in activatio

of t he ma mma lia n egg. Rev. Reprod. 3, 96103.

Berridge, M . J . (1991). C yt oplasmic calcium oscillationsA tw

pool model. C e l l C a l c i u m 12, 6372.

168 Stephen A . Str ick e

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

13/20

Berridge, M. J. (1993). Inositol t risphosphate an d calci um signall ing.

N a t u r e 361, 315325.

Bezprozvann y, I . , and Ehrlich, B. E. (1995). The inositol 1,4,5-

trisphosphate (InsP 3) receptor. J. M em br. B io l . 145, 205216.

Bird, G . S. J . , and Putney, J . W. (1996). Effect of inositol 1,3,4,5-

tetrakisphosphate on inositol trisphosphate-activated Ca 2 sig-

n a li n g i n m o u se l a cr im a l a c in a r c el ls . J. B i o l . C h em . 271,

67666770.

B loom, T. L . , Szut s , E. Z . , a nd Eckberg, W. R . (1988). I nos it ol

trisphosphate, inositol phospholipid metabolism, and germinal

vesicle breakdown in surf clam oocy tes.D ev. B io l .129, 532540.

Brown e, C. L. , Creton, R., Karplus, E., Moh ler, P. J ., Pala zzo, R. E. ,

and Miller, A. L. (1996). Analysis of the calcium transient at NEB

during the fi rst cell cycle in dividin g sea urchin eggs.B i o l . B u l l .

191, 516.

Brow nlee, C ., and D ale, B. (1990). Tem poral and spatia l correlati on

of fert i l iza t ion current , ca lcium w a ves a nd cyt opla s mic cont ra c-

tion in eggs of C i o n a i n t e st i n a l i s. Proc. Roy. Soc. London Ser. B

239, 321328.

Buck, W. R., Ra kow , T. L., and Shen , S. S. (1992). Syn ergistic release

of calcium in sea urchin eggs by caffeine and ryanodin e.Exp. Cell

Res.202, 5966.Busa, W. B., Ferguson, J . E. , Joseph, S. K., Williamson, J . R. , and

Nuccitelli, R. (1985). Activation of frog (Xenopus laevis) eggs by

inos it ol t r is phos pha t e. I . C ha ra ct eriza t ion of C a 2 release from

intracellular st ores. J. Cell Biol. 101, 677682.

Busa, W. B., and Nuccitelli, R. (1985). An elevated free cytosolic

C a 2 w a v e f o l l ow s f er t il i z at i o n i n e gg s o f t h e f ro g, Xenopus

laevis. J. Cell Biol. 100, 13251329.

C arroll, D . J., Albay, D . T., Terasaki, M ., Jaffe, L. A., and Foltz , K. R.

(1999). I dent ifi ca t i on of P L C -dependent a nd -independent

event s during fert i l iza t ion of s ea urchin eggs . D e v . B i o l . 206,

232247.

C a r ro ll , D . J. , R a m a r ao , C . S ., M e hl m a n n, L. M . , R o c h e, S .,

Terasaki, M., and Jaffe, L. A. (1997). Calcium release at fertiliza-tion in starfi sh eggs is mediated by phospholipase C .J. Cell Bi ol.

138, 13031311.

C arroll, J. , and Sw ann, K. (1992). Spontaneous cytosolic calcium

oscillations driven by in ositol trisphosphat e occur during i n v i t r o

ma t ura t ion of mous e oocyt es .J. Biol. C hem . 267, 1119611201.

C arroll, J. , Sw ann, K., Whitt ingham , D ., and Whita ker, M. (1994).

Spatiotem poral dynam ics of intracellular [C a 2]i oscillations dur-

ing t he grow t h a nd m eiot ic ma t ura t ion of mous e oocyt es.D evel-

opment 120, 35073517.

C heek, T. R . , M cG uinness , O. M . , V incent , C . , M oret on, R . B . ,

B erridge, M . J. , a nd Johns on, M . H. (1993). Fert i l is a t ion a nd

t him eros a l s t imula t e s im ila r ca lcium s piking pa t t erns in m ous e

oocyt es but by dif ferent mecha nis ms . D evelopm ent 119, 179

189.

C hiba , K. , Ka do, R . T. , a nd Ja f fe, L . A . (1990). D evelopment of

ca lcium relea se m echa nisms during s t a rfi s h oocyt e ma t ura t ion.

Dev. B io l . 140, 300306.

Chini, E. N. , L ia ng, M . Y. , a nd Dous a , T. P . (1998). Dif ferent ia l

e f fe c t o f p H o n c y c l i c -A D P - ri b o se a n d n i c o t i n a t e a d e n i n e

dinucleotide phosphate-induced C a 2 release system s. B iochem .

J. 335, 499504.

C lapper, D . L. , Walseth, T. F. , D argie, P. J ., an d Lee, H . C . (1987).

P yridine nucleot ide met a bolit es s t imula t e ca lcium relea se from

s ea urchin egg micros omes desens it ized t o inos it ol t r is phos -

phate. J. Biol. Chem. 262, 95619568.

C onley, E. C . , and Bramm er, W. J. (1998). The Ion C hannel Facts

Book. Voltage-G ated C hannels. Academic P ress, San D iego.

Creton, R., and Jaffe, L. F. (1995). Role of calcium infl ux during th

latent period in sea urchin fertilization. D ev . G r o w t h . D i f f er .37

703709.

C reton, R., Speksnijder, J. E., and Jaffe, L. F. (1998). Pa tt erns of fre

calcium in zebrafi sh embryos. J. Cell Sci. 111, 16131622.

Csutora, P. , Zhengchang, S. , Kim, H. Y., Burgim, A., Cunningham

K. W., Nuc cit elli, R., Keizer, J. E., Ha nley , M. R., and Blal ock, J. E

(1999). Calcium infl ux factor is synthesized by yeast and mam

ma lia n cells deplet ed of orga nella r ca lcium s t ores . Proc. NatA cad. Sci. U SA 96, 121126.

Dale, B. (1988). Primary and secondary messengers in the activatio

of ascidian eggs. Exp. Cell Res. 177, 205211.

D ale, B. , and D eFelice, L. (1990). Soluble sperm factors, electrica

events and egg activa tion. I n Mechanism of Fertilization: Plan t

to Humans (B. Dale, Ed.), pp. 476487. Springer Verlag, Berlin

D eguchi, R., and Morisaw a, M . (1997). Spatial patterns of in crease

in int ra cellula r ca lcium a t fert i l iza t ion in oocyt es of t he m a rin

bivalve M yt i lus edul i s. J. Reprod. D ev. 43(Suppl.), 183184.

D eguchi, R., and O sanai, K. (1994a). Meiosis reinitiat ion from th

fi rst prophase is dependent on the levels of int racellular Ca 2 a n

p H i n o o cy t e s o f t h e b i v a l v es M a ct r a c h i n en si s a n d L i m a r i

hakodatensis . D ev. B i o l . 166, 587599.Deguchi, R., and Osanai, K. (1994b). Repetitive intracellular Ca 2

increases at fertilization and the role of Ca 2 in meiosis reinitia

tion from t he fi rst metaphase in oocyt es of ma rine bivalves.De

B i o l .163, 162174.

D eguchi, R . , a nd Os a na i , K. (1995). Serot onin-induced meios i

reinitiation from t he fi rst prophase and from the fi rst m etaphas

i n o o cy t e s o f t h e m a r i n e b i v al v e H i at ell a flacci da : Respectiv

cha nges in int ra cellula r Ca 2 a nd pH. Dev. B io l . 171, 483496

D eguchi, R . , Os a na i , K. , a nd M orisa w a , M . (1996). Ext ra cellula

C a 2 e n t r y a n d C a 2 release from inositol 1,4,5-trisphosphate

sensitive stores function at fertilization in oocytes of the marin

bivalve Myt i lus edul is . Development 122, 36513660.

D e K o ni n c k, P . , a n d S ch u l m a n , H . (1 99 8). S en s it i v i t y o f C a M

k in a se II t o t h e f re qu en c y o f C a 2 oscillations. Science 279227230.

D e n g , M . Q . , a n d Fa n , B . Q . (1 99 6). I nt r a ce ll u la r C a 2 durin

f er t i li z a t io n a n d a r t ifi c i a l a c t i v at i o n i n m o u s e o o cy t e s. A c t

Pharm . S in ica17, 357360.

Deng, M . Q. , Hua ng, X. Y. , Ta ng, T. S. , a nd Sun, F. Z . (1998)

S po n t a n e o us a n d f er t i l iz a t i o n -i n d u c ed C a 2 o s c il l a t i o n s i

mous e imma t ure germina l ves icle s t a ge oocyt es . Biol. Reprod

58, 807813.

D e Young, G . W., and Keizer, J . (1992). A single-pool in osito

1,4,5-trisphosphate receptor-based model for agonist-stimulate

os cil la t ions in Ca 2 concentration. Proc. Natl. Acad. Sci. U SA

89, 98959899.

D ow d, D . R. (1995). C alcium regulation of apoptosis.I n Ca lciumRegulat ion of C ellular Funct ion (A. R. Mean s, Ed.), pp. 255280

Raven Press, New York.

D ube, F. , a nd G uerrier, P. (1982). Activation of Barnea candid

(M ollus ca , P elecypoda ) oocyt es by s perm or KCl, but not b

N H 4Cl, requires a calcium infl ux. Dev. B io l . 92, 408417.

D upont, G . (1998). Link betw een fertilizat ion-induced C a 2 osci

lations an d relief from m etaphase II arrest in ma m ma lian eggs: A

model based on calmodulin-dependent kinase II activation. Bio

phys. Chem . 72, 153167.

Dupont, G . , McG uinness, O. M., Johnson, M. H., Berridge, M. J

a nd B orgese, F. (1996). P hos pholipa s e C in mous e oocyt e

C ha ra ct eriza t ion of a n d isoforms and t heir possible involve

ment in sperm-induced calcium spiking. Bioch em . J. 316, 583

591.

16Fert i l i zat i on-Induced C a2 Signals

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

14/20

Eckberg, W. R., an d Anderson, W. A. (1995). C yt oskeleton , cellula r

s igna ls , a nd cyt opla smic loca liza t ion in Chaetopterus embryos.

Curr . Top. D ev. B io l . 31, 1995.

Eckberg, W. R., and C arroll, A. G . (1982). Sequestered calcium

t r i gg er s o o cy t e m a t u r a t i on i n Chaetopterus. C el l D i f fer . 11,

155160.

Eckberg, W. R., and Miller, A. L. (1995). Propagated and nonpropa-

ga t ed ca lcium t ra ns ient s during egg a ct iva t ion in t he a nnelid,

Chaetopterus. Dev. Biol. 172, 654664.Eckberg, W. R., Miller, A. L., Short, L. G ., and Jaffe, L. F. (1993).

C a lcium puls es during t he a ct iva t ion of a prot os t ome egg. B io l .

B u l l .185, 289290.

Eisen, A., Kiehart , D . P., Wieland, S. J., and R eyn olds, G . T. (1984).

Tempora l s equence a nd s pa t ia l dis t r ibut ion of ea rly event s of

fertilization in single sea urchin eggs.J. Cell Biol .99, 16471654.

Eisen, A., and Reynolds, G . T. (1984). Calcium transients during

ea rly development in s ingle s t a rfi s h (Asterias forbesi) oocytes.

J. Cell Biol. 99, 18781882.

Epel, D . (1990). The initiat ion of development at fertilization. Cel l

Di f fer . Dev. 29, 112.

Eva ns, J. P . , a nd Kopf, G . S. (1998). M olecula r mecha nis ms of

spermegg interactions and egg activation. Andrologia 30, 297307.

Ferguson, J . E. , Han, J . K., Kao, J . P. Y., and Nuccitelli, R. (1991).

The effects of inositol trisphosphates and inositol tetrakisphos-

ph a t e o n C a 2 relea s e a nd Cl current pa t t ern in t he Xenopus

laevis oocyt e. Exp. Cell Res. 192, 352365.

Fissore, R. A., Dobrinsky, J . R. , Balise, J . J ., D uby, R. T., and Robl,

J. M . (1992). P a t t erns of int ra cellula r C a 2 concent ra t ions in

fertilized bovine eggs. Biol. Reprod. 47, 960969.

Fis sore, R . A ., G ordo, A . C . , a nd Wu, H. (1998). A ct iva t ion of

development in m a mm a ls : I s t here a role for a s perm cyt os olic

factor? Theriogenology 49, 4352.

Fissore, R. A., Longo, F. J., Anderson, E., Parys, J. B., and D ucibella ,

T. (1999). Differential distribution of inositol trisphosphate re-

ceptor isoforms in mouse oocytes. Biol. Reprod. 60, 4957.Fissore, R. A., Pinto-Correia, C. , and Robl, J . M. (1995). Inositol

trisphosphate-induced calcium release in the generation of cal-

cium oscillations in bovine eggs. Biol. Reprod. 53, 766774.

Fis sore, R . A ., a nd R obl, J . M . (1994). M echa nis m of ca lcium

oscillations in fertilized rabbit eggs. Dev. B io l . 166, 634642.

Fluck, R. A., M iller, A. L. , and Jaffe, L. F. (1991). Slow calcium

w a ves a ccompa ny cy t okinesis in meda ka fi s h eggs . J. Cell Biol.

115, 12591265.

Fluck, R. A., Miller, A., and Jaffe, L. F. (1992). High calcium zones

at the poles of developing medaka eggs. B i o l . B u l l . 183, 7077.

Foltz, K. R. (1995). Sperm-binding proteins. I n t . R e v . C y t o l . 163,

249303.

Foltz, K. R., and Shilling, F. M. (1993). Receptor-mediated signalt ra ns duct ion a nd egg a ct iva t ion. Zygote1, 276279.

Fong, P. P. , D eguchi, R., and Kyozuka, K. (1997). C haracterization

of serotonin receptor mediating int racellular calcium increase in

meiosis-reinitiated oocytes of the bivalve Rudi t apes phi l ippina-

ru m from central Japan. J. Exp. Zool. 279, 89101.

Fontanilla, R. A., and N uccitelli, R. (1998). C haracterization of th e

s perm-induced ca lcium w a ve in Xenopus eggs us ing confoca l

microscopy. Bi ophy s. J. 75, 20792087.

Freema n, G ., and Ri dgw ay , E. B. (1987). Endogenous phot oproteins,

calcium channels and calcium transients during metamorphosis

in hydrozoa ns. Rouxs Arch. Dev. B io l . 196, 3050.

Freema n, G ., and Rid gw ay, E. B. (1991). Endogenous phot oproteins

as calcium indicators in hydrozoan eggs and larvae. Zool. Sci. 8,

225233.

Freeman, G . , an d Ridgw ay, E. B. (1993). The role of intracellula

ca lcium a nd pH during fert i l iza t ion a nd egg a ct iva t ion in t h

hydrozoan P h i al i d i u m . D e v . Bi o l . 156, 176190.

Fujiw ara, A., Taguchi, K., an d Yasuma su, I . (1990). Fertilizatio

mem brane form ation in sea urchin eggs induced by drugs know

t o ca us e Ca 2 release from isolated sarcoplasmic reticulum. De

G r o w t h . D i f f e r. 32, 303314.

Fujiw ara, T., N akada, K., Shirakaw a, H ., and M iyazak i, S. (1993

Development of inositol trisphosphate-induced calcium releas

mecha nis m during ma t ura t ion of ha ms t er oocyt es . D e v . B i o

156, 6979.

G a lione, A ., Jones, K. T. , L a i , F . A ., a nd Sw a nn , K. (1997). A

cytosolic sperm protein factor mobilizes Ca 2 from intracellula

s t ores by a ct iva t ing mult iple Ca 2 release m echanisms indepen

dently of low -molecular-w eight m essengers. J. Biol. C hem . 272

2890128905.

G alione, A., Lee, H. C., and Busa, W. B. (1991). Ca 2-induced C a 2

relea s e in s ea urchin egg homogena t es : M odula t ion by cycli

ADP-ribose. Science253, 11431146.

G alione, A., McDougall, A., Busa, W. B., Willmot, N., G illot, I., an

Wh i t a k e r, M . (1 99 3). R e d u n da n t m e c h a n i s m s o f c a l c i u m

induced calcium release underlie calcium w aves during fertilization of sea urchin eggs. Science261, 348352.

G alione, A., and Summerhill, R. (1996). Regulation of ryanodin

receptors by cyclic ADP-ribose. I n Ryan odine Receptors (V

Sorrentino, Ed.), pp. 5170. CRC Press, Boca Raton.

G a ll ica no, G . I ., Schw a rz , S. M . , M cG a ughey, R . W. , a nd Ca pco

D . G . (1993). Protein kinase C , a pivota l regulator of ha mst er eg

activa tion, function s after elevation of intracellular free calcium

Dev. B io l . 156, 94106.

G eilenkirchen, W. L. M., Jansen, J . , C oosen, R., an d v an Wijk, R

(1977). C hanges in t he content of cyclic AM P an d cyclic G MP i

eggs ofM actra sol id i ssim aduring the second cleavage cycle. Ce

Biol . In t . Rep. 1, 419426.

G enazzani, A. A., a nd G alione, A. (1997). A C a2

release mechanis m ga t ed by t he novel pyridine nucleot ide, NA A DP . Trend

Pharm . Sci. 18, 108110.

G ilbert , S. F. (1994). D evelopment al Biology, 4th ed. Sina ue

Sunderland.

G i lkey, J. C. (1981). M echa nis ms of fert i l iza t ion in fi s hes. A m

Z o o l . 21, 359375.

G ilkey, J. C ., Jaffe, L. F., Ridgw ay , E. B., and Reyn olds, G . T. (1978

A free ca lcium w a ve t ra vers es t he a ct iva t ing egg of t he m eda k

O ryzias lat ipes. J. Cell Biol . 76, 448466.

G illot , I . , and Whitaker, M . (1993). Ima ging calcium w aves in egg

a nd em bryos. J. Exp. Biol. 184, 213219.

G la hn, D . , M a rk, S. D . , B ehr, R . K. , a nd Nuccit ell i , R . (1998

Tyrosine kinase inh ibitors block sperm-induced egg activat ion i

Xenopus laevis. Dev. Biol. 205, 171180.

G obet, I . , Durocher, Y., Leclerc, C. , Moreau, M., and G uerrier, P

(1994). Reception and transduction of the serotonin signal re

sponsible for meiosis reinitiation in oocyt es of the Japanese clam

Ruditapes phi l ippinarum. Dev. B io l . 164, 540549.

G obet, I . , Lippai, M., Tomkow iak, M ., Leclerc, C. , M oreau, M., an

G uerrier, P. (1995). 4-Aminopyridine acts as a w eak ba se and

ca lcium mobiliz ing a gent in t r iggering m eiosis reinit ia t ion a n

activation in the Japanese clam Rud i t apes phi l ippinarum . Int .

Dev. B io l . 39, 485491.

G oudeau, H., and G oudeau, M. (1998). Depletion of intracellula

C a 2 s t o re s, m e d i a t ed b y M g 2-stim ulated InsP 3 l ibera t ion o

thapsigargin, induces capacitative Ca 2 infl ux in prawn oocytes

Dev. B io l . 193, 225238.

170 Stephen A . Str ick e

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

15/20

G oudeau, M., and G oudeau, H. (1993). In the egg of the ascidian

Ph a l l u si a m a m m i l l a t a , remova l of ext erna l Ca 2 modifi es t he

fert i l iza t ion pot ent ia l , induces polys permy, a nd blocks t he re-

s umpt ion of meios is. Dev. B io l . 160, 165177.

G oudea u, M . , a nd G oudea u, H. (1996). Ext erna l M g 2 triggers

oscillations an d a subsequent sustain ed level of intracellular free

C a 2, correla t ed w it h cha nges in m embra ne conduct a nce in t h e

oocyt e of t he pra w n Palaem on serratu s. D ev. Biol .177, 178189.

G ould, M ., and Stephano, J . L. (1989). H ow do sperm a ctivat e eggs

in U rechis (as w ell as in polych aetes and m olluscs)? I n Mecha-

nisms of Egg Activation (R. Nuccitelli, G . N. Cherr, and W. H.

Clark, Eds.), pp. 201214. Plenum Press, New York.

G ould, M . C ., and Stephano, J . L. (1996). Fertilizat ion and parthe-

nogenesis in U rechi s caupo (Echiura). I nv. Repr. D ev.30, 1722.

G rum ett o, L., Wildin g, M., D e Simon e, M. L., Tosti, E., G alion e, A.,

and Dale, B. (1997). Nitric oxide gates fertilization channels in

a s cidia n oocyt es t hroughout nicot ina mide nucleot ide met a bo-

lis m. B iochem . Biophys. Res. Com m un. 239, 723728.

G u, X. , a nd Spit zer , N . C. (1995). D is t inct a s pect s of neurona l

differentiation encoded by frequency of spontaneous Ca 2 t ra n-

sients. N a t u re 375, 784787.

G uerrier, P. , Durocher, Y., G obet, I . , Leclerc, L. , and Moreau, M.(1996). Reception and transduction of the serotonin signal re-

sponsible for meiosis reinitiation in bivalves. Inv. Repr. Dev. 30,

3945.

G uerrier, P., Leclerc-D avid, C ., and M oreau, M . (1993). Evidence for

t he involvement of int erna l ca lcium s t ores during s erot onin-

induced meios is reinit ia t ion in oocyt es of t he biva lve mollus c

R u d i t a p es p h i l l i p i n a ru m . D ev . B i o l . 159, 474484.

Ha fner, M . , P et zelt , C. , N obiling, R . , P a w ley, J. B . , Kra mp, D . , a nd

Schatt en, G . (1988). Wave of free calcium at fertilization in t he

s ea urchin egg vis ua lized w it h fura -2. C e l l M o t i l . C y t o s k e l . 9,

271277.

Ham aguchi, Y., and H am aguchi, M. S. (1990). Simult aneous inves-

t iga t ion of int ra cellula r C a2

increase and morphological eventsupon fertilization in the sand dollar egg. Cel l . Struct . Funct. 15,

159162.

Han , J . K., a nd N uccitelli, R. (1990). Inositol 1,4,5-trisphosphate-

induced calcium release in the organelle layers of the stratifi ed,

int a ct egg of Xenopus laevis. J. Cell Biol. 110, 11031110.

Harris, P. J. (1994). Caffeine-induced calcium release in sea urchin

eggs and the effect of continuous versus pulsed applications on

t he m it ot ic a ppa ra t us . Dev. B io l . 161, 370378.

Hartzell, H. C., Machacha, K., and Hirayama, Y. (1997). Effects of

adenophostin-A and inositol-1,4,5-trisphosphate on Cl currents

in Xenopus laevisoocytes. M o l . Ph a r m . 51, 683692.

Harvey, E. B. (1939). D evelopm ent of half-eggs of Chaetopterus

pergamentaceus w it h s pecia l reference t o pa rt henogenet ic m e-

rogony. B i o l . B u l l . 76, 384404.

He, C . L . , D a mia ni, P . , P a rys , J . B . , a nd Fis sore, R . A . (1997).

C a lcium, ca lcium relea se recept ors , a nd meiot ic res umpt ion in

bovine oocytes. Biol. Reprod. 57, 12451255.

Herbert, M ., M urdoch, A. P. , and G illespie, J . I . (1995). The thiol

reagent, th imerosal, induces intracellular calcium oscillation s in

ma t ure huma n oocyt es . M o l . H u m . R ep r od . 10, 21832186.

Hertzler, P. L. , and C lark, W. H. (1992). C leavage and gastrulation

in t he s hrimp Sicyonia ingentis: Invagination is accompanied by

oriented cell division. D evelopm ent 116, 127140.

Hill, T. D., Berggren, P.-O., and Boynton, A. L. (1987). Heparin

inhibit s inos it ol t r isphospha t e-induced ca lcium relea se from

permeabilized rat liv er cells.B iochem . Biophys. Res. Com m un.

149, 897901.

Hinega rdner, R . (1975). Ca re a nd ha ndling of s ea urchin egg

embryos a nd a dult s (principa lly Nort h A merica n s pecies ). I

The Sea U rchin Embryo. Biochemistry and M orphogenesis (G

C ziha k, Ed.), pp. 1025. Springer Verlag, Berlin.

Hiram oto, Y., Yoshim oto, Y., an d Iw am atsu, T. (1989). Increase i

intracellular calcium ion s upon fertilization in anim al eggs.A c t

H i st o c h em . C y t o c h em . 22, 153156.

Igusa, Y., and Miyazaki, S. (1983). Effects of altered extracellula

a nd int ra cellula r ca lcium concent ra t ion on t he hyperpola riz in

responses of the ham ster egg.J. Physiol. 340, 611632.

Ikegami, S. , Okada, T. S. , and Koide, S. S. (1976). On the role o

c a l c iu m i o n s i n o o c y t e m a t u r a t i on i n t h e p ol y c h a et

Chaetopterus pergamentaceus. D ev. Grow th . D i f fer .18, 3343

I w a m a t s u, T. (1992). Egg a ct iv a t ion (in J a pa nes e). F i sh B i o

J. M edaka 4, 110. [For English version, see ht tp://biol1.bio

nagoy a-u.ac.jp:8000/Iw am at suT92.htm l]

Iwa ma tsu, T. (1997). Abbreviation of the second m eiotic divisio

by precocious fert i l iza t ion in fi s h oocyt es . J. Exp. Z ool . 277

450459.

Iwa ma tsu, T., Kikuyam a, M ., and H iramot o, Y. (1992). Fertilizatio

rea ct ion w it hout cha nges in int ra cellula r Ca 2 in medaka eggs

An experiment w ith acetone-treated eggs. D e v . G r o w t h D i f f e34, 709717.

Iwa m atsu, T., and Oht a, T. (1978). Electron microscopic observa

tion on sperm penetration and pronuclear formation in the fi s

egg. J. Exp. Zool. 205, 157180.

Iw am at su, T., Oht a, T., Osh im a, E., and Sugiura, T. (1985). Requi re

m e n t o f e xt r a ce ll u la r c a l ci u m i o n s f o r t h e e a rl y f er t i li z a t i o

event s in t he m eda ka egg. D ev . G r o w t h . D i f f er . 27, 751762.

Iwa ma tsu, T., On itake, K., Yoshim oto, Y., and Hiram oto, Y. (1991

Time sequence of early events in fertilization in t he medaka egg

D e v . G r ow t h D i f f er . 33, 479490.

I w a ma t s u, T. , Yos himot o, Y. , a nd Hira mot o, Y. (1988). M echa

nis ms of Ca 2 release in medaka eggs microinjected w ith in osito

1,4,5-trisphosphate and Ca2

. Dev. B io l . 129, 191197.Jaffe, L. A. (1990). First m essengers at fert iliza tio n. J. Reprod. Fert i

Suppl. 42, 107116.

Jaffe, L. F. (1983). Sources of calcium in egg activation: A review

and hypothesis. Dev. B io l . 99, 265276.

Jaffe, L. F. (1985). The role of cal cium explosions, w aves a nd pulse

in activ ating eggs.I n Biology of Fertilization (C . B. Metz and A

Monroy, Eds.), pp. 127165. Academic Press, New York.

Jaffe, L. F. (1990). The roles of int ram em brane ca lcium in polariz in

a nd a ct iva t ing eggs . I n M echa nis m of Fert i l iza t ion: P la nt s t

Humans (B. Dale, Ed.), pp. 389417. Springer Verlag, Berlin.

Ja f fe, L . F. (1991). The pa t h of ca lcium in cyt os olic ca lcium

oscillations: A unifying hypothesis. Proc. Natl. Acad. Sci. U SA

88, 98839887.

Jaffe, L. F. (1995). C alcium w aves an d development. I n Ca lcium

Wa ves, G ra dient s a nd Os cil la t ions (R . B ock a nd K. A ckril

Eds.), pp. 4 17. Wiley, C hich ester.

Johnson, J., Bierle, B. M., G allica no, G . I., and C apco, D . G . (1998

C alcium /calm odulin dependent protein kinase II and calmodu

lin: Regulators of the meiotic spindle in mouse eggs. D ev . B i o

204, 464477.

Johns t on, R . N. , a nd P a ul, M . (1977). Ca lcium infl ux follow in

fertilization of U rechis caupo eggs. Dev. B io l . 57, 364374.

Jone s, K. T. (1998). C a 2 oscillations in the activa tion of the egg an

development of t he embryo in ma mma ls . In t . J. D ev. B io l . 42

110.

Jones, K. T., Carroll, J . , Merriman, J . A., Whittingham, D. G . , an

Kono, T. (1995a). Repetitiv e sperm-induced C a 2 t ra ns ient s i

17Fert i l i zat i on-Induced C a2 Signals

Copyright 1999 by Academic Press. All rights of reproduction in a ny form reserved.

5/25/2018 1-s2.0-S0012160699993405-main

16/20

m o u s e o o cy t e s a r e c e l l c y c l e d ep en d en t . Development 121,

32593266.

Jones, K. T., C arroll, J ., an d Whittin gham, D . G . (1995b). Ionom y-

cin, t h a psiga rgin, rya nodine, a nd s perm induced C a 2 release

increa s e during meiot ic ma t ura t ion of mous e oocyt es . J. Biol.

C h e m .270, 66716677.

Jones, K. T. , a nd Whit t ingha m, D . G . (1996). A compa ris on of

sperm-induced and IP 3-induced Ca2 relea s e in a ct iva t ed a nd

aging mouse oocytes. Dev. B io l . 178, 229237.Jones, K. T., Crutt w ell, C . , Parrington, J . , and Sw ann, K. (1998a). A

mammalian sperm cytosolic phospholipase-C activity generates

inositol trisphosphate and causes Ca 2 release in sea urchin egg

homogenates. FEBS Lett. 437, 297300.

Jones, K. T., Soeller, C ., and C ann ell, M . B. (1998b). The passage of

C a 2 a nd fl uores cent ma rkers bet w een t he s perm a nd egg a f t er

fus ion in t he m ous e. D evelopm ent 125, 46274635.

Juneja, R., I to, E. , and Koide, S. S. (1994). Effect of serotonin and

tricyclic antidepressants on intracellular calcium concentration

in Spisula oocytes. C e l l C a l c i u m 15, 16.

Juneja, R., a nd Koide, S. S. (1996). Biochemica l path w ays involved

in serotonin-regulated Spisula oocyt e ma t ura t ion a nd fert i l iza -

t ion. I nv. Repr. D ev. 30, 4753.Ka da m, A . L . , Ka da m, P . A ., a nd Koide, S. S. (1990). C a lcium

requirement for 5-hydroxyt rypt a m ine-induced m a t ura t ion of

Spisula oocytes. I n t . J. I nv. Repr. Dev.18, 165168.

Keating, T. J., Cork, R. J., and Robinson, K. R. (1994). Intracellular

free ca lcium os cil la t ions in norma l a nd clea va ge-blocked em-

bryos and artifi cially act ivated eggs ofXenopu s laevis. J. Cell Sci.

107, 22292237.

Kimura, Y., Yanagim achi, R., Kuretake, S., Bortkiewicz , H., Perry,

A. C. F. , and Yanagimachi, H. (1998). Analysis of mouse oocyte

activation suggests the involvement of sperm perinuclear mate-

rial. Biol. Reprod. 58, 14071415.

Kline, D. (1988). Calcium-dependent events at fertilization of the

frog egg: Injection of a calcium buffer blocks ion channel open-ing, exocyt os is, a nd forma t ion of pronuclei . D e v . B i o l . 126,

346361.

Kline, D. (1996). Activation of the mouse egg. Theriogeneology 45,

8190.

Kline, D ., and Kline, J. T. (1992a). Repetitiv e calcium tran sient s and

the role of calcium in exocytosis and cell activation in th e mouse

egg. Dev. B io l . 149, 8089.

Kline, D ., and Kli ne, J. T. (19