Placental Vascular Corrosion Cast Studies: A ComparisonBetween Ruminants and HumansRUDOLF LEISER,1* CHRISTIANE KREBS,1 BRIGITTE EBERT,1 AND VIBEKE DANTZER2

1Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, D-35392 Giessen, Germany2Department for Anatomy and Physiology, Royal Veterinary and Agricultural University Copenhagen,DK-1870 Frederiksberg C, Denmark

KEY WORDS villous placenta; bovine; sheep; goat; human; blood circulation; corrosion cast

ABSTRACT The microvasculature of both the ruminant placentomes of cattle, sheep, and goatsand the human placenta were compared, using corrosion casts of blood vessels and scanning electronmicroscopy. The fetal vascular trees of ruminant and human placenta differ in form and size, whichcorrelates with the degree of ramification; however, their architecture of stem, intermediate, andterminal villi is similar. In the human, the system of serially linked capillary convolutions ofterminal villi is longer than that in ruminants. Therefore, in guaranteeing blood flow against flowresistance, the human vessels particularly need a straight course, anastomoses, and sinusoidaldilations. Specifically in the ruminants studied, the venous vessels outweigh the arterial ones byvolume and by number. They are suggested to be absorptive for substances metabolized in the zoneof the capillary complex. The most extreme interspecies difference relates to the maternalvasculature, which, in contrast to the fetal system, is a closed system in the ruminant septas and anopen lacunal intervillous space in the human. Converging and differing morphological vascularphenomena of ruminants and human placenta are discussed in terms of maternofetal exchangerelated to placental efficiency. In summary, the ruminant placenta, concerning the fetal vasculartree, in many aspects is workable as a model for the human. Microsc. Res. Tech. 38:76–87,1997. r 1997 Wiley-Liss, Inc.

INTRODUCTIONAn extraordinary variability of placental structures

has been developed throughout the mammalian spe-cies. The ruminant and the human placentas are notphylogenetically closely related (Starck, 1959; Moss-man, 1987); however, astonishingly, their placentas areof a structurally similar villous type (for review, seeLeiser and Kaufmann, 1994). In both, chorioallantoicvillous trees build up to fetal placental cotyledons. Inruminants, one cotyledon penetrates the maternal sep-tal system of an endometrial caruncle, both togetherforming one of numerous placentomes. In the human,cotyledons protrude into the extendedmaternal intervil-lous blood space of the single polycotyledonary placen-tal disc.Because of this tight penetration of the cotyledons

into the caruncles, for a long time the villous tree couldnot be isolated and shown in a three-dimensional wayin ruminants, whereas the villosity of the humanplacenta, being free floating in maternal blood, couldeasily be demonstrated by stereological microscopy(overview by Boyd and Hamilton, 1970) or scanningelectron microscopy (Kaufmann et al., 1979). Finally, inthe goat, there was a methodological possibility to showthree dimensionally the fetal placenta to be villiform inshape by using microcorrosion casts from blood vessels(Leiser, 1987). In addition, this method also allowed thereplication of the architecture of maternal septal vascu-lar systems in the goat separately from that of the fetalvilli. In the human, however, the maternal placentalpart could not be treated that way for ethical reasons.

In this study, scanning electron microscopy of corro-sion casts was used to compare the similar ruminantand human placental vasculatures morphologically.Their function and the possible value of the ruminantplacenta as a model for the human are also discussed.

MATERIALS AND METHODSNear-term placentas, three from the cow, four from

the sheep, and six from the pygmy goat, were studiedand compared with four human placentas from uncom-plicated pregnancies, gently removed from uteri bycaesarean sections. In addition, to show the placentomein overview, one bovine placenta was examined fromthe fourth month of pregnancy (see Fig. 2A).In the cow, placentas were perfused with buffer to

remove blood immediately after slaughter. The sheepand goats were under general anesthesia (Rompun 1mg/kg body weight, intramuscularly; and Ketalar 5mg/kg body weight, intramuscularly) when the perfu-sion was performed. The human placentas were rinsedin warm (37°C) physiological saline before buffer perfu-sion.The phosphate buffer (0.1 M, pH 7.3) for perfusion in

all species was warmed to 37°C, and 1,000 UI/literheparin as anticoagulant and 0.5% procaine for vasodi-lation were added. Additionally, muscular contractionand postvitam degeneration of the vessel walls were

*Correspondence to: Prof. Dr. R. Leiser, Institute for Veterinary Anatomy,University of Giessen, Frankfurter Strasse 98, D-35392 Giessen, Germany.Received 28 February 1995; Accepted 15 May 1995

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r 1997 WILEY-LISS, INC.

suppressed by a second perfusion with ice-cold (4°C)buffer and immersion of the whole organs in the samebuffer for 2 hr. This cooling also effected two otherpoints: minimizing extravasation of the plastic (seebelow) into the interstitium through increased rigidityof the vessels and delay of polymerization of the plastic,allowing it to harden completely.Batson No. 17 compound (Polysciences) mixed with

Sevriton (De Trey Dentsply, D-Konstanz, Germany)33:12 were used as plastic components (see Leiser andKohler, 1983; Leiser, 1985). The mass was freshlyprepared and cooled before instillation, thus preventingpolymerization for about 10 min. This time was suffi-cient to instill the plastic with a syringe under manualpressure at a flow rate of about 5 ml/min.It was very important to use the same batch of each of

the prepared plastic component mixtures for one castonly and to inject it into the maternal (uterine) or fetal(umbilical) arteries as close as possible to the chosenplacental area. This guaranteed that the mass wouldstill be in its initial liquid stage (viscosity of about 20 P;see Leiser, 1985) to distribute itself smoothly in fillingthe vessel system uniformly and subsequently wouldpolymerize homogeneously. Arteries and veins wereclamped after instillation to prevent efflux of plasticand to hold the pressure of instillation in the system.Then, the whole placenta of the instilled part wasplaced in a water bath at 20°C for 30 min, followed by awater bath at 80°C for 4 hr to allow hardening of theplastic.Corrosion of instilled placental tissue was performed

by alternative immersion in 40% KOH and distilledwater at 60°C. The liquids were changed at least twiceper day until they were no longer opaque and theyellow-white casts became visible. To obtain suitablepieces for mounting, large pieces of the casts wereembedded in warm 20% gelatin (50°C) and cooled to-5°C for cutting with a knife. Very smooth fractures(Figs. 2A, 3B, 6B) of these gelatin-immersed casts wereachieved by cracking in liquid nitrogen. After thawing,the gelatin was removed by a second corrosion proce-dure. Although the gelatin treatment certainly had acleaning effect, the corroded casts also needed verythorough and repeated washing at room temperature indistilled water, with 5% Extran (Merck) and distilledwater again in order to dissolve all remnants of tissueand remove them from the very dense microvascula-ture.Suitable specimens of the cut or cracked, air-dried

casts were selected by stereomicroscopy and mountedon stubs using conductive carbon cement. Finally, thespecimens were dried (or stored) in a dust-free desicca-tor and sputter coated with gold (3 nm), before scanningelectron microscopy was performed.

RESULTSThe overview of the placentomal ruminant and dis-

coid human placental villous trees is schematized inFigure 1. Because of the differing shape of the placent-omes, being mushroom-like in cattle (Fig. 9A) andcup-like in the sheep and goat (Figs. 1A, 9B), thegeneral form of a single villous tree, in cattle, is conical,large on its base, and thinning out to its top like aChristmas tree (Fig. 9A), whereas, in sheep and goat, it

is cylindrical, like a poplar tree (Figs. 1A, 9B). Thehuman villous tree is roundish or globular (Fig. 1B).

Maternal Vascular PhenomenaSpiraling in the course of maternal vessels can be

observed in ruminants and in humans.Mainly in cattle,the bulk of the caruncular stalk consists mostly of large,vigorously spiraled arteries and veins (Fig. 2A), whichare interwoven into smaller vessels of the caruncularbase or basal plate. From this base, septal arteriesramify towards the placentome, initially showing aslightly spiraling course. This feature is typical forsmall ruminants (Figs. 1A, 2B). In the human, spiralarteries ‘‘show a marked spiral twisting’’ (Boyd andHamilton, 1970), while penetrating through the basalplate and opening into the intervillous space (Fig. 1B).The latter is bordered by trophoblast, thus defining theplacental blood lacuna.Perivascular capillaries develop with an alternating

pattern of ramification along arteries and veins of thebovine uterus or caruncular stalk, respectively (Fig.4A). In the human uterus, such capillaries also can beobserved, here constituting poorly developed nets (Be-nirschke and Kaufmann, 1990). These capillary nets,however, cannot be classified as the same as the para-vascular networks of the fetal placental villous tree (seebelow).

Fetal Vascular PhenomenaThe general architecture of the fetal villous tree,

defined in the human placenta to be subdivided intosegments of stem villi, intermediate villi, and terminalvilli (Kaufmann et al., 1979; Kaufmann, 1982; Fig. 1B),can be observed in the ruminants too (Fig. 1A). Accord-ing to this classification, the vessels also can be de-scribed as stem arteries and veins, intermediate arteri-oles and venules, and terminal capillaries, as in thehuman (Kaufmann et al., 1985; Leiser et al., 1985) andin the goat (Leiser, 1987). Stem arteries and veins caneasily be distinguished on casts by the impressions ofthe endothelial cells, which are slender and longitudi-nally oriented in the artery and roundish and randomlyoriented in the vein (Figs. 3, 4B). Intermediate arteri-oles and venules can be recognized less well by theseimpressions. In addition, they are more twisted anddistinctly smaller than stem vessels; they form bridgesto or from terminal capillaries (Fig. 3). On paravascularand terminal fetal capillaries (see below), endothelialimpressions are often missing; however, capillaries areconspicuous by their roundish diameter and their gener-ally convoluting course (Figs. 3, 8). The venous system,particularly venules and veins, outweighs the arterialsystem in ruminants in number and volume comparedto the human, where these systems are rather bal-anced. The capillary complex is distinctly less dense inruminants than in humans (cf. Fig. 3Awith Fig. 3B). Ingeneral, the type of ramification is more acutely angledin ruminants, whereas it tends to show obtuse angles inthe human (Fig. 3).The relationship of arterial to venous arrangement

and the number of different segments of the villous treediffers between the two kinds of villous placenta: In theruminants, stem villi of the upper order (e.g., ramifica-tion steps 6–8 in cattle) with one artery, centrallylocated, can be observed. Peripherally it is accompanied

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by several veins, which have a slightly convergentcourse towards the fetal side of the placentome (Fig. 5).In general, this vascular pattern can be observed in theintermediate villus too: venules peripherally accompa-nying a single arteriole. However, in this case, they aremore numerous (up to eight) and converge more than inthe stem villi (Fig. 3A). In the neck of the terminal villi,which is generally short (Fig. 6A), one arterial limb,situated in the center of the terminal capillary system,often meets a few venous capillary limbs in parallel(Fig. 1A). The orientation of terminal villi with respectto the main axis of the villous tree in general shows anangle of about 45° (Figs. 3A, 5, 7A).In the human, the ramification order of stem vessels

goes up to about 16 (Leiser et al., 1991). In the lower

orders, it is represented by one artery and one vein only(Fig. 3B). In the upper orders, including the intermedi-ate villus and neck of terminal villi (Figs. 3B, 6B), a fewarteries and veins or arterioles and venules (up to threeeach) are involved in balanced numbers. Generally, thecourses of these vessels are parallel or slightly twistedaround each other (Fig. 6B). The arterioles and venulesof intermediate villi normally lead to the arterial andvenous capillary limb in the necks of terminal villiwithout any intersection (Fig. 6B). The vessels of thesenecks tend to be conspicuously long in the human (Fig.7B).A paravascular capillary network (Boe, 1969; Kauf-

mann et al., 1988; Leiser et al., 1985) develops along thestem and intermediate vessels in the human (Fig. 4B).

Fig. 1. Schematic drawings of placental overview and vesselarrangement. A: Goat. Two placentomes from the multicotyledonaryplacenta show numerous fetal villous trees dipping into crypts formedby maternal endometrial septae (dotted). The course of the fetal (fa;white) as well as the maternal (ma; black) arteries and arterioles (top)brings the two—fetal (white or stippled) and maternal (hatched)—capillary systems (bottom) into close apposition. The fetal systemshows asymmetrically arranged capillary loops consisting of a shorter,more centrally situated arterial limb (fa) and a longer, superficialvenous capillary limb (fv). Basket-like maternal capillaries surroundthe fetal capillary convolutions and generally exhibit a vertical orfetouterine direction of blood flow. In spite of the fact that there arecross-current conditions inside each villous/cryptal unit, the overallarrangement comes close to that of a countercurrent flow. Bothcapillary nets show a serial arrangement of capillary loops in a such

way that the first capillary loops of the fetal side are opposed to the lastseptal capillaries of the maternal side. B: Human. In the disc-shapedplacenta, villous trees are projecting from the chorion plate (black)into the intervillous blood space. Each villous tree forms a fetalcotyledon, irrigated by a fountain-like blood stream (hatched arrows).This blood stream is fed by spiral arteries (ma) and flows back intoveins (mv), both situated in the basal plate (stippled). This flowarrangement represents the multivillous or pool flow condition whenmeeting the fetal villosity. Note the branching system of an intermedi-ate villus and terminal villi including a fetal arteriole (fa) and a fetalvenule (fv), which are bridged by three serially linked capillaryconvolutions of terminal villi. Note: With the exceptions of Figures 2Aand 4A, all casts refer to the near-term (ruminants) or term (human)stages. Modified from Dantzer et al. (1988) with permission of thepublisher.

78 R. LEISER ET AL.

Some capillaries of this network are singled out intypical hairpin-like loops. In the ruminants, paravascu-lar capillaries can be observed only sporadically nearterm, without any net formation.Capillary convolutions, each corresponding to one

terminal villus, project from the neck region or from oneintermediate villus (Fig. 8), in a somewhat fan-shapedpattern in the ruminants (Figs. 7A, 8A) and irregularlyin the human (Figs. 7B, 8B). Serially interconnected ontheir bases, they number up to five in ruminants (Figs.1A, 8A) and up to six in the human (cf. Fig. 8B). In theformer, series of a total length of about 1,000 µm can beestimated; for the latter, Kaufmann et al. (1985) mea-sured 5,000 µm.Measuring on casts, however, is particu-larly complicated by coiling of the capillaries, which areespecially tortuous in the near-term bovine placenta(Fig. 7A). In contrast, the human capillaries of terminalvilli are conspicuously lengthened by anastomoses (Fig.8B). Therefore, the capillary complex in total appearsvery compact (Fig. 7B). Sinusoidal dilations can beobserved in both ruminants and human terminal capil-lary convolutions (Figs. 7B, 8A), but they are morepronounced in the latter.

DISCUSSIONDefinition of Placental Efficiency

in Relation to Vascular ArchitectureThe efficiency of a placental type is reflected by the

ratio of weight of neonate and placenta to some extent;e.g., it shows howmany grams of fetus are produced per1 gram of placenta at term (Table 1). The ratio rangesfrom 6:1 in the human to 20:1 in the guinea pig: Theruminants can be found in the middle range, such assheep or goat with 10:1 and cow with 13:1 (Dantzer etal., 1988; Kaufmann, 1990). The neonate to placentaweight ratio correlates with the amount of substancetransferred with the maternofetal diffusional ex-change, e.g., oxygen and/or carbon dioxide, as defined intheoretical models by physiologists (for review, seeFaber and Thornburg, 1983). In morphological terms,this depends on, and in part can be deduced from, thegeometric arrangement of maternal and fetal vessels ofthe placental exchange area, predominantly capillaries(Dantzer et al., 1988; Mossman, 1987), or blood flowdirections, respectively. The existingmaternofetal inter-relating principles studied on placental vascular corro-sion casts are multivillous or pool flow, cross-current

Fig. 2. Maternal spiral arteries. A: Cow (fourth month of gesta-tion). Cracked overview cast of placentomal caruncle and caruncularstalk. Narrowly spiraling arteries and veins of the central caruncularstalk area (star) reach the dense connecting vasculature of thecaruncle base (CB), from which stem vessels radiate to form septae

(arrows), which end in peripherally located capillary complexes (CC).375.B: Sheep. Connecting arteries of the caruncular base (CA) ramifyinto septal arteries (arrows), which start with a slightly spiralingcourse. The septal capillary complex (CC) is partly filled by plastic,whereas the veins are not filled at all. 3165.

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Fig. 3. Overview of fetal villous trees, with stem villous arteries(SA) and veins (SV), intermediate villous arterioles (IAl) and venules(IVl), and terminal villous capillary convolutions (CC). A: Goat. Ingeneral, the tree is shaped like a poplar, and its vasculature shows amoderate density. The venous system, particularly venules and veins,

is more conspicuous than the arterial system. The capillary convolu-tions often appear somehow flattened (bottom left). 3170. B: Human.The cracked cast demonstrates a tree, globular in shape, with a densevasculature comprising a balanced number of arterial and venouscomponents. 3220.

80 R. LEISER ET AL.

and countercurrent (Table 1), recorded in increasingefficiency of exchange (Leiser et al., 1989; Leiser andKaufmann, 1994; Leiser and Koob, 1992).

Ruminant and HumanMaternofetalVascular Interrelationship in Termsof General Structure and Blood Flow

Ruminants and humans both show a conspicuouslysimilarmultivillous vasculature, as seen in the architec-ture of the fetal villous tree (Figs. 1, 3). However, thedistinct variability of neonate to placenta weight ratioamong these species—small in human and moderate inruminants (see above)—must depend on a differinggeneral structural interrelationship of the vasculature(Table 1).In the ruminant placentomes, the structural interre-

lationship of both the relatively small-caliber vessels ofcaruncular septas and the fetal cotyledonary villi isclosed, without any formation of lacunas. This meansthat the blood streams in a strictly determined way(Leiser andKoob, 1992).Also, the very effective counter-current course can partly be found (see above). Becausematernal as well as fetal stem arteries reach out to thefetal and the maternal sides of the placentome, both thecapillary networks become oriented in opposite ways.On the other hand, the capillary systems meet insideeach cryptal (septal) villous unit, providing the less

efficient cross-current blood flow condition (Fig. 1A,Table 1).In the human placental disc, the maternal blood

circulates in a jet-like fashion, preventing a strict andsmooth course through the complex, vastly extended,lacunal intervillous space (Ramsey and Donner, 1980).Thematernal vessel system therefore is open, in opposi-tion to the ‘‘canalized,’’ regularly flowing blood in thevasculature of the ruminant fetal villous tree. In termsof blood flow, as recorded above, this condition repre-sents the least efficient multivillous or pool flow type(Fig. 1B, Table 1).

Size and Shape of the Villous Tree in Relationto theArrangement of Capillary ComplexesCompared Between the Ruminants Studied

and the HumanCapillary complexes are the location of the most

intensive maternofetal exchanges (Benirschke andKaufmann, 1990; Kaufmann et al., 1979). For maximalefficiency, the placenta, or the villous tree, must containcapillary complexes, ‘‘exchange areas,’’ as voluminousas possible within the tree. The ‘‘supplying’’ part of it,including arteries/veins and arterioles/venules, how-ever, has to be as small as possible; e.g., particularlyvenules and veins ought to be short, for allowing a quick

Fig. 4. Peri-/paravascular capillary systems.A:Cow (fourth monthof gestation). Perivascular capillaries of a maternal artery of thecaruncular stalk ramify with an alternating pattern (arrows), thusrepresenting vasa vasorum. 3500. B: Human. Hairpin-like fetalcapillary loops (arrowheads) frequently accompanying the stem artery(A) and stem vein (V) are typical of a paravascular capillary system.This system has been removed partly by preparation of the specimen.3280.

Fig. 5. Relation of number and arrangement of arterioles andvenules in the sheep. A stem villus ramifies into two intermediate villi(arrows) in a typical way. One artery (A) or arteriole (AI) situated inthe center of a villus is peripherally accompanied by several veins (V)or venules (VI). Terminal villi are obliquely oriented (arrowheads)with respect to the main direction of the stem axis, and their venouscapillary limb systems (VC) are peripherally located. 31,150.

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expulsion of the oxygenated blood from the capillarybed to the fetus. This system therefore works better invillous trees of small size (Fig. 9; Table 1). The effect caneven be reenforced if the degree of ramification of thesevessels is low.Hence, it seems to be true that, the larger the term

ruminant placentomes or human placenta, the smallerthe effect for substantial exchange. The degree of vesselramification, which, remarkably, is of a similar frac-tional type (random segment branching) in sheep(Eibenstein et al., 1994) and humans (Kosanke et al.,1993), shows the same relationship. This is reflected bythe fact that the average distance between chorionicand basal plate is 15 mm in sheep or goat, 20 mm incattle, and 30 mm in human. The numbers of ramifica-tion orders of supplying vessels of the villous treecorrelate as well: four to six in sheep or goat, eight toten in cattle, and up to 16 in human (Table 1; Leiser etal., 1991).The shape of the villous tree, however, reduces the

influence of tree size and the degree of ramification. Inthe sheep or goat, because of the cup-like form of theplacentome (Fig. 9B), the villous unit is predominantlylong and cylindrical, reminiscent of a poplar tree. Itexhibits relatively long supplying vessels and a rather

small capillary complex, being active for substancetransfer, in the periphery. Because the bovine placent-ome is formed like a mushroom, it exhibits a Christmastree-like shape of the villous unit (Fig. 9A). This favorsshort routes of supply for the rather voluminous capil-lary complex (cf. Tsutsumi, 1962). In the human globu-lar form of the villous tree, larger areas of capillarycomplexes can be found. The supplying part is alsorelatively large, with long vessels (Table 1). Thesephenomena influence the function of the placental unitin an optimally balanced way. Because of the impor-tance of the volume ratio of working part to supplyingpart of the villous tree, a dependence of the placentalefficiency, reflected in the neonate to placental weightratio (human six, sheep/goat ten, cow 13), cannot beexcluded.

Comparison of Vascular Features Promoting(Maternofetal) Substance Exchange inCapillaries of Terminal Villi and in

Arterioles/Venules of Intermediate VilliThe terminal capillary system inside the terminal

villi of the villous tree includes arterial capillary limbsand venous capillary limbs, connected by capillaryloops or capillary convolutions. These convolutions are

Fig. 6. Straight and parallel courses of capillary limbs. A: Goat.Generally, one arterial limb (AL) and several venous limbs (VL) of aterminal villus run parallel in a straight, short course. Note the highlyanastomosed and dense pattern of the capillaries. 3800. B: Human.

Cracked cast through a complex of an intermediate villus withtributary terminal villi (top to bottom). One arteriole (IAl) and twovenules (IVl) of the intermediate villus are typically long and straight,without any sharp demarcation from the terminal villi (arrow). 3170.

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serially linked two to five times in ruminants and up tosix times in humans (Table 1). The total length of thiscapillary system can reach up to 1,000 µm in cattle(Leiser, unpublished) and 5,000 µm in humans as

measured by Kaufmann et al. (1985) and Leiser et al.(1991). These authors suggested that capillary sinu-soids, being numerous and reaching diameters up to 60µm in the human, prevent a standstill of the blood flowafter the law of Hagen-Poiseuille. This is convincingwhen compared to the ruminant placenta. Because thecapillary system is much shorter, sinusoidal dilationsare much less conspicuous in size and number. Sinu-soids located near the villous tips may also support theconclusion of Arts (1961) that sinusoids locally slow theblood flow, providing an opportunity for maternofetalexchange (Table 1). Anastomoses, as with sinusoids,can also offer more capillary luminal space in a givensystem, such as the terminal capillary system, allowingthe blood to flow by a decrease in flow resistance. Eventhough anastomoses are not easy to trace out three-dimensionally in vessel casts, again they are distinctlymore numerous in the human than in ruminants,supporting the statementmade above (Table 1). Anasto-moses are more pronounced in cattle than in sheep orgoat. This probably can be explained by the longergestation time of the former, because this phenomenondevelops progressively throughout pregnancy, as hasbeen observed in other placental types (Leiser andKoob, 1992).In a given volume of terminal villi, the capillary

density or the capillary luminal space becomes en-hanced by coiling of capillary convolutions. Therefore,the capillary luminal surface increases its absorptivecapacity, favoring maternofetal substance exchange(Table 1). The coiling is most pronounced, typicallytortuous, in cattle in the last month of pregnancy, whichmay show that the placenta of this species is stretchingthe given volume to its limits. The coiling of terminalcapillaries is irregular but less dense in the human.However, for an unquestionable qualification of thecoiling phenomenon in terms of substance transfer—orcapillary luminal surface and volume in general—astereologic morphometric examination of the villoustree using histology has been done only in the human(see overview in Luckhardt et al., 1995).Conspicuously, arterial and venous capillary limbs of

the terminal capillary system can often be observed instraight, parallel courses. This phenomenon is morefrequent in the human, where it is also extended intosome parts of the intermediate villi. Obviously, thisvessel course transfers the blood to the capillary convo-lutions—the location of the most effective maternofetalexchange (Kaufmann et al., 1979)—in the shortest waypossible, preventing an unnecessary decrease in bloodpressure because of increased flow resistance (see alsoabove; Table 1). Some rediffusion of substances (O2)through the thin-walled venous limb to the arterialcapillary limb cannot be excluded, because of their closeneighborhood, favoring the most effective countercur-rent blood flow.Arterioles and venules of intermediate villi relate

differently to each other in number and arrangement inthe species studied (Table 1): The centroarteriolar-peripherovenular model in ruminants (Fig. 1A; onearteriole surrounded by up to eight extremely thin-walled venules) represents a countercurrent blood flowcondition. The conspicuously voluminous venular sys-tem slows the blood flow back to the fetus. Under theseconditions, reabsorption of substances, as discussed

Fig. 7. Coiling and anastomosing of terminal villi. A: Cow. Thecoiling found in near-term pregnancy, particularly in the cow, is denseand often meandering. Stem artery (SA), stem vein (SV), intermediatearteriole (lAI), intermediate venule (IVl), and five terminal villi (1–5).3700. B:Human. Irregular coiling, with little anastomosing. Note thefrequent occurrence of sinusoidal dilations on the extremities ofcapillary loops (arrowheads). The intermediate arteriole (IAl) ramifiesinto three terminal villi (arrows), of which the few arterial (AL) andvenular (VL) capillary limbs are rather long. 3880.

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above in terminal villi, may happen here as well.However, the voluminous venular system probablytends to give this system a specific function; e.g.,hormones produced by the placenta (Reimers et al.,1985; Wooding, 1992) might be transported back toplacental targets as discussed for the pig by Reynolds etal. (1985) and Dantzer and Leiser (1993). In the human,this system is less conspicuous: One arteriole is irregu-larly arranged with a few (up to three) venules (see alsoKaufmann et al., 1985).

Para- and Perivascular Capillary NetworksThe paravascular fetal capillary network, located

along stem and intermediate vessels of the villous tree,is distinct in the human but can be observed onlysporadically near term in ruminants. Because it existsthroughout pregnancy in the human, Boyd and Hamil-ton (1970) and Leiser et al. (1985) described it ‘‘to besimply a residual indication of better vascularization inearlier stages of development’’ (see also Kaufmann,1982; Kaufmann et al., 1988). In the ruminants, thosefew capillaries might represent perivascular capillariesin the sense of a ‘‘vasa vasorum.’’ The stem vesselsmight need an additional supply for vascular nourish-ment as they become relatively large near term (Table1). This indicates that the general development ofcapillaries of the villous tree (Castellucci et al., 1989) isa different scheme, probably depending on the mater-nofetal blood stream conditions being closed in rumi-nants or open in the human placenta (see above).Perivascular capillaries are common in arteries andveins of the caruncle stalk of ruminants, especially inthe cow. These vessels are particularly thick-walled andobviously need ‘‘vasa vasorum,’’ because of mechanicalpush and pull stresses by the fetus (see also below). Inthe human, such a phenomenon, albeit poorly devel-oped, has been mentioned by Benirschke and Kauf-mann (1990).

Spiraling VesselsMaternal spiral arteries are located in the basal plate

of the placenta in the human and in the placentomalstalks in ruminants. In the human, they have been ofinterest for a long time, because they curb the bloodpressure and flow to the intervillous space by spiralingand by cytotrophoblastic plugs in their origins (seeoverview by Boyd and Hamilton, 1970; Benirschke andKaufmann, 1990; Schneider and Luckhardt, 1989). Incontrast to the case in the human, representing theopen maternofetal blood stream arrangement (seeabove), the impact of blood flow by spiraling may play aminor role in the closed arrangement of ruminants.Here, with spiraling being most pronounced in thespecifically thick-walled arteries and veins of the car-uncle stalk of the bovine (see above), the arrangementmight also work in the sense of bedsprings, when thecaruncle stalks become flexed by movements of thefetus and the mother.

Could Vascular Phenomenaof the Ruminant Villous PlacentaWork as a Model for the Human?

For ethical reasons the human placenta can gener-ally be investigated morphologically only at birth.Therefore, with respect to microvascular research dur-

Fig. 8. Serially linked terminal villi. A: Cow. Highly anastomosingcapillaries in the neck region (top area) of three terminal villi beingserially bridged (dashed lines). A fourth terminal villus obviously is ina stage of growth (arrow). Note the increase in the caliber of thecapillaries towards the terminal loops, which becomes evident asso-called sinusoidal dilations (asterisks). 31,200. B: Human. Ratherloosely arranged and long branching system of five, serially intercon-nected (arrowheads) terminal villi. 31,200.

84 R. LEISER ET AL.

ing almost all the stages of pregnancy, animal modelsare needed. In many respects, the ruminant placenta(see above and Table 1) is similar to the human one andso it may, at least partly, meet these needs. Both speciesrepresent a villous placental type, which is particularlyreflected by the architecture of the fetal villous tree,with stem, intermediate, and terminal vessels. Thelatter include the capillaries, which are the most impor-tant unit for exchange. In developing series consisting

of up to five convolutions, the ruminant capillarycomplex does not differ greatly from the human termi-nal capillary system with up to six convolutions perseries (Kaufmann et al., 1985; Leiser et al., 1991).Because this system is distinctly longer in the humanthan in the ruminant species, the former needs moremorphological features to guarantee blood flow againstflow resistance, e.g., straight course, anastomoses, sinu-soidal dilations. Both species show a venular/venous

TABLE 1. Developmental degree of vascular phenomena related to efficiency (moderate 1, distinct 11) in comparing near-term villousplacentae of ruminants (cow, sheep, goat) and humans

Phenomenon

Expression of phenomenon inPositive placental efficiency (maternofetal

substance exchange) related to vascular phenomenon

Ruminants Humans Ruminants Humans

Weight ratio of neonat (i)to placenta

Cow: 13:1Sheep/goat: 10:1

6:1 11 1

Maternofetal blood flowinterrelationship

Mixture of cross-currentand countercurrent

Multivillous (pool flow) 11 1

General structural mater-nofetal vascular inter-relationship

Closed (without lacunaformation)

Open (with lacuna forma-tion)

11In dependence on mater-nofetal blood flow inter-relationship (see phe-nomenon listed above)

1

General shape of fetalvillous tree

Cow: conical (like aChristmas tree inmushroom-like placen-tome; see Fig. 9)

Sheep/goat: cylindrical(like a poplar tree incup-like placentome;see Fig. 9)

Globular (‘‘bushy’’; seeFig. 1B)

11 11Depends on size and relation of supplying part(arteries/veins, arterioles/venules) vs.substance-exchanging part (capillarycomplex) of the villous tree (see Discussion)

Degree of fetal vesselramification

Cow 8–10 ordersSheep/goat 4–6 orders

Up to 16 orders

Length of fetal terminalvilli capillary system,including number ofserially linked convolu-tion

Up to 1,000 µmCow: 3–5 convolutionsSheep/goat: 2–3 convolu-tions

Up to 5,000 µmUp to 6 convolutions

11 11The relation of blood pressure vs. length ofcapillary system is smoothed or stressed byspecificities such as parallel straight course,coiling, anastomosing, and sinusoidaldilatations (see phenomena listed below)

Degree of straight courseand parallelism of arte-rial and venous capil-lary limbs in terminalcapillary system

Moderate (arterial andvenous limbs are rathershort)

Distinct (also extendedinto parts of interme-diate villi)

1/2 11Blood is transported inthe shortest way pos-sible to/from capil-laries, preventing flowresistance

Degree of coiling in fetalcapillary convolutes

Cow: distinct (particu-larly near term)

Sheep/goat: moderate

Individually irregular(increasing towardsterm)

11Absorptive luminal sur-face of capillaries isenhanced

1

Degree of anastomosinginside fetal capillaryconvolutes

Cow: distinctSheep/goat: moderate

Very distinct 1 11Blood flow resistance decreases by increasedtotal luminal space of capillaries

Sinusoidal dilatations incapillaries

Moderate (particularlytowards term)

Capillary diameter up to45 µm

Distinct (increasing from30th week of preg-nancy)

Capillary diameter up to60 µm

1 11Local increase of capillary luminal spaceeffects the blood to flow with reducedflow resistance

Arrangement and rela-tion of number of fetalarterioles to venules inintermediate villi

One centrally locatedarteriole is surroundedby up to eight venules

One arteriole irregularlyarranged, with a few(up to 3) venules

11The centroarteriolar-pe-ripherovenular rela-tionship of countercur-rent blood flowprobably favors reab-sorption of substances(hormones) in venules

1

Paravascular fetal capil-lary system (locatedalong stem and inter-mediate vessels)

Paravascular systemsparsely develops alongarteries and veins mea-suring 100 µm or morein diameter in secondhalf of pregnancy

Distinct 1/2 11Discussed as a relic of theterminal capillary net-work in early preg-nancy

85RUMINANTS AND HUMAN PLACENTAL VASCULATURE

system outweighing the arterial/arteriolar one; how-ever, in the ruminants it is more distinct, which sug-gests the reabsorption of substances (see above, Dantzerand Leiser, 1993).The most extreme interspecies difference relates to

the maternal vasculature, which, in contrast to thefetal system, is closed in the ruminant septae and openin the human lacunal intervillous blood space. Thisfavors placental efficiency, with an increased neonate toplacentaweight ratio in the ruminants, obviously depen-dent on the blood flow conditions (see above). Therefore,these conditions must be considered when carrying outresearch on fetal andmaternal placental components incombination.

ACKNOWLEDGMENTSWe thank Mrs. Susanne Schubert-Porth and Ms.

Alexandra Hax for their outstanding technical assis-tance.

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Fig. 9. Simplified scheme of a ruminant placentome. Left sectorsshow maternal septal tissue (S; densely stippled); middle sectorsrepresent a combination of septae and chorionic villous trees (SVT). Inthe right sectors, villous trees can be found consisting of a peripheralcapillary complex or ‘‘working part’’ (smoothly stippled) and thecentrally located connective tissue (CT) as a ‘‘supporting part.’’ Endo-metriumwith uterine glands (UG) andmyometrium (M).A:Mushroom-like shape of placentome in the cow. The form of the villous tree is

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