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1 Updated:12/3/12 Pregnancy Loss and Parturition John Parrish Updated:12/3/12 Distribution of Prenatal Losses Fertilization 100% » Under optimal conditions 2/3 loss during embryonic development » Imprinting » Compaction » Blastocyst hatching and formation » Failure to prevent CL regression Maternal recognition of pregnancy Updated:12/3/12 Distribution of Prenatal Losses (cont.) 1/3 loss during fetal stage » Crowding » Placental insufficiencies » Not the fetus directly Updated:12/3/12 Embryonic and Fetal Loss in Cattle 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 5 Calving Pregnancy Loss Interval From Breeding (months) Percentage Updated:12/3/12 Embryonic and Fetal Loss in Pigs 10 12 14 16 18 20 0 25 40 0 20 40 60 80 100 Number Survival (%) Stage of Gestation (days) Number of CLs, Embryos or Fetuses Present % Survival Updated:12/3/12 Increased Prenatal Loss Nutritional Stress » Energy shortages » Mineral imbalances » Vitamin deficiencies Disease of the reproductive tract Endocrine imbalances Aging of gametes prior to fertilization

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1!

Updated:12/3/12

Pregnancy Loss and

Parturition!

John Parrish!

Updated:12/3/12

Distribution of Prenatal Losses!•  Fertilization 100%!

» Under optimal conditions!•  2/3 loss during embryonic development!

» Imprinting!» Compaction!» Blastocyst hatching and formation!» Failure to prevent CL regression !

•  Maternal recognition of pregnancy!

Updated:12/3/12

Distribution of Prenatal Losses (cont.)!•  1/3 loss during fetal stage!

» Crowding!» Placental insufficiencies!» Not the fetus directly!

Updated:12/3/12

Embryonic and Fetal Loss in Cattle!

0102030405060708090100

0 1 2 3 5 Calving

Pregnancy Loss

Interval From Breeding (months)!

Perc

enta

ge!

Updated:12/3/12

Embryonic and Fetal Loss in Pigs!

10

12

14

16

18

20

0 25 400

20

40

60

80

100Number Survival (%)

Stage of Gestation (days)!

Num

ber o

f CLs

, Em

bryo

s or

Fe

tuse

s Pr

esen

t!

% S

urvi

val!

Updated:12/3/12

Increased Prenatal Loss!•  Nutritional Stress!

» Energy shortages!» Mineral imbalances!» Vitamin deficiencies!

•  Disease of the reproductive tract!•  Endocrine imbalances!•  Aging of gametes prior to fertilization!

2!

Updated:12/3/12

Effect of Oocyte Age on Fertilization and Embryo Viability!

0

20

40

60

80

100

0 4 8 12 16 204

6

8

10

12

% O

ocyt

es

Fert

ilize

d N

orm

ally!

Viab

le E

mbr

yos

at 2

5 D

ays

of P

regn

ancy!

Age of Oocyte at Fertilization!Updated:12/3/12

Parturition!

Updated:12/3/12

Mechanism For Parturition

 Skunk Cabbage!  Prolonged gestation in Sheep"  hypoplasia of Anterior Pituitary

 Gene Defect"  Autosomal recessive in Holstein cattle"  Large calves, 1-2 months beyond due date"  hypoplasia of Anterior Pituitary"

Updated:12/3/12

Fetal Adrenal Changes with Age!

Fetal Age!

Adr

enal

Gla

nd W

eigh

t!

Parturition!

Change in Adrenal Size is a Response to Stress!!!

• Lack of space!• Lack of gas exchange!• Lack of nutrients!

Updated:12/3/12

Hormonal Changes Associated with Parturition!

Updated:12/3/12

Parturition!Fetal Nutritional!

Demands!

Placental!Insufficiency!

Hypothalamus! Anterior!Pituitary!

Adrenal !Cortex!

CRH! ACTH!

Fetal Corticosteroids!(Cortisol)!

3!

Updated:12/3/12

Parturition!Fetal Nutritional!

Demands!

Placental!Insufficiency!

Hypothalamus! Anterior!Pituitary!

Adrenal !Cortex!

CRH! ACTH!

Fetal Corticosteroids!(Cortisol)!

Lung!(surfactant)!

Liver!(glycogen)!

Thyroid!(metabolism)!

Progesterone! Estrogen! PGF2α!

Placentome!

Updated:12/3/12

Parturition!Fetal Nutritional!

Demands!

Placental!Insufficiency!

Hypothalamus! Anterior!Pituitary!

Adrenal !Cortex!

CRH! ACTH!

Fetal Corticosteroids!(Cortisol)!

Lung!(surfactant)!

Liver!(glycogen)!

Thyroid!(metabolism)!

Progesterone! Estrogen! PGF2α!

Uterine!Contractions!

PGF2α

Relaxin!

Oxytocin!

Uterine Endometrium!»  Oxytocin receptors!

Uterine Myometrium!»  Gap junctions!

Ovary!(CL)!

Cow,Sow!Triggers!

CL!Regression!

Placentome!

Cervical!Ripening!

Updated:12/3/12

Final Role of Oxytocin!Sensory Neurons in Cervix!

Oxytocin from!Posterior Pituitary!

Myometrial!Contractions!

Updated:12/3/12

Orientation of Fetus!•  Fetus must reorient prior to parturition!

» Initially on back!» Reorient so feet and head will exit first!» Breech!

•  Rear of fetus comes first!

• Orientation not important in pig!•  Abnormal orientation results in dystocia!

Updated:12/3/12

Fetal Orientation!

Updated:12/3/12

Fetal Orientation!

4!

Updated:12/3/12

Stages of Labor!•  Preparative (2 to 12 hours)!

» Myometrial contractions!» Uterine pressure!» Abdominal discomfort!» Cervical dilation!

Updated:12/3/12

Stages of Labor (cont.)!•  Expulsion of fetus (30 to 180 min)!

» Strong uterine contractions!» Rupture of the allantochorion!» Appearance of the amnion!» Maternal recumbence and straining!» Not only uterine but abdominal contractions

as well!» Rupture of the amnion and delivery!

Updated:12/3/12

Stages of Labor (cont.)!•  Expulsion of the placenta (1 to 12 hours)!

» Uterine contractions!» Chorionic villi loosen!» Expulsion of the placenta!» Delayed in ruminants due to presence of

cotelydons separating independently!» Suckling induces oxytocin release which

triggers further uterine contractions!

Updated:12/3/12

Dystocia!•  Difficult birth!•  Excessive fetal size (90% for cattle)!•  Abnormal presentations (5% for cattle)!• Multiple births (twins)!

» Twins presented at the same time!» One is usually blocking the other!» Uterus becomes fatigued!

Updated:12/3/12 Updated:12/3/12

5!

Updated:12/3/12 Updated:12/3/12

Dystocia!

Updated:12/3/12

Perinatal Fetal Changes!•  Cardiovascular!

» Ductus arteriosis!» Foramen ovale!» Ductus venosus!

Updated:12/3/12

Placenta!

Liver!

Left Atrium! Lungs! Right Atrium!

Foramen!Ovale!

Ductus!Venosus!

Ductus!Arteriosus!Aorta!

Umbilical Arteries!

Umbilical Vein!

Portal Vein!

Vena Cava!

Head!and !

Heart! Tissues!

Fetal Circulatory!System!

Updated:12/3/12

Liver!

Left Atrium! Lungs! Right Atrium!

Foramen!Ovale!

Ductus!Arteriosus!Aorta!

Portal Vein!

Vena Cava!

Head!and !

Heart! Tissues!

Ductus!Venosus!

Transitional!Circulatory!

System!

Updated:12/3/12

Liver!

Left Atrium! Lungs! Right Atrium!

Foramen!Ovale!

Ductus!Arteriosus!Aorta!

Portal Vein!

Vena Cava!

Head!and !

Heart! Tissues!

Transitional!Circulatory!

System!

Ductus!Venosus!

6!

Updated:12/3/12

Liver!

Left Atrium! Lungs! Right Atrium!

Foramen!Ovale!

Ductus!Arteriosus!Aorta!

Portal Vein!

Vena Cava!

Head!and !

Heart! Tissues!

Transitional!Circulatory!

System!

Ductus!Venosus!

Updated:12/3/12

Liver!

Left Atrium! Lungs! Right Atrium!

Foramen!Ovale!

Ductus!Arteriosus!Aorta!

Portal Vein!

Vena Cava!

Head!and !

Heart! Tissues!

Transitional!Circulatory!

System!

Ductus!Venosus!

Updated:12/3/12

Liver!

Left Atrium! Lungs! Right Atrium!

Foramen!Ovale!

Ductus!Arteriosus!Aorta!

Portal Vein!

Vena Cava!

Head!and !

Heart! Tissues!

Transitional!Circulatory!

System!

Ductus!Venosus!

Updated:12/3/12

Liver!

Left Atrium! Lungs! Right Atrium!

Foramen!Ovale!

Ductus!Arteriosus!Aorta!

Portal Vein!

Vena Cava!

Head!and !

Heart! Tissues!

Transitional!Circulatory!

System!

Ductus!Venosus!

Updated:12/3/12

Liver!

Left Atrium! Lungs! Right Atrium!

Foramen!Ovale!

Ductus!Arteriosus!Aorta!

Portal Vein!

Vena Cava!

Head!and !

Heart! Tissues!

Adult!Circulatory!

System!

Ductus!Venosus!

Updated:12/3/12

Perinatal Fetal Changes!•  Cardiovascular!

» Ductus arteriosis!» Foramen ovale!» Ductus venosus!

•  Thermoregulatory!» Must regulate own temperature!» Increase metabolism (thyroid activity)!» Brown fat - metabolism of produces heat!

•  Energy metabolism!» Until suckling, relies on own stores of

glycogen!

7!

Updated:12/3/12

Perinatal Fetal Changes (cont.)!•  Immune status!

» Has no antibodies to protect!» Gets passive immunity from mother!

•  Gut permeable to antibodies in colostrum!•  Only first 1 - 2 days!•  In rabbit, rat, man get some antibodies absorbed

through placenta!

Updated:12/3/12

Parturition!

Conception!

Postpartum

Involution(2 - 3 weeks)!

Uterus!

Myometrium!

Shrinkage and

atrophy!

Endometrium!

Repair!

Lumen!

Elimination of bacteria!

Hypothalamus!

Anterior Pituitary!

Ovaries!

Steroids! Follicles!

Estrous Cycles (4 to 10 weeks)!

Updated:12/3/12

Return to Estrus!•  Fertility increases with # of estrous

cycles!» First = 35% pregnancy rate!» Second = 50%!» Third = 73%!» Fourth = 72%!

•  Lactational anestrus or Lactational amenorhea!

Updated:12/3/12

Return to Estrus (cont.)!•  Special postpartum estrus!

» Mare - foal heat, 6 - 13 days postpartum!•  Fertility depends on body condition!

» Sow!•  Anovulatory estrus 3 - 5 days post-farrowing!•  Weaning induces estrus 3 - 5 days latter!

Updated:12/3/12

Retained Placenta!•  Definition!

» If not expelled within 24 hr it may be retained for 5 - 6 days !

• Most common in cattle (5 - 15 %)!» Not seen in sows or ewes!» Sometimes seen in mares (retained = > 4 hrs)!

Updated:12/3/12

Equine Retained Placenta!

8!

Updated:12/3/12

Retained Placenta (cont.)!•  Cause!

» Normally get lack of blood flow to chorionic villi and this causes them to regress!

» High incidence in premature or early delivery!» High milk producers!» Twins!» Dystocia!» Induction of parturition!» Nutritional deficiencies!

•  Vitamin A!•  Selenium!

Updated:12/3/12

Retained Placenta (cont.)!•  Treatment!

» Manual removal not recommended!» Daily antibiotics!» Large single antibiotic bolus!» Oxytocin or PGF!

• Major concerns in humans and mares!» Can cause death of mother from septicemia!

Updated:12/3/12

Induction of Parturition!•  Dexamethazone!

» Potent synthetic cortisol!» Works in all species!» Takes 2 to 3 days!

•  PGF2α!» Swine, cattle and sheep!

• Oxytocin!» Human, horse!

Review Remaining Slides for Species Specific Procedures! ! Updated:12/3/12

Cow - Do not induce before last 7-14 Days of gestation

Method: Dexamethasone - parturition in 48 hours, 20-50 mg/IM

-High incidence of retained placentas and lower postpartum fertility (severity increases the earlier induced).

Azium (trade name) combined with 25 mg Lutalyse induces within 35+2 hours. Requires a live fetus to work and does not work on a mummified fetus

- Retained placenta is not problem if treated properly - Giving estrogen before induction of parturition incidence

Prostaglandins used in cases of a mummified fetus and are also effective in inducing abortion the first 4-5 months

Updated:12/3/12

Sheep - Best within a few days of parturition

Dexamethasone (8-20 mg) Parturition in 24-72 hours

Retained placenta not a problem

Can use Lutalyse to abort before Day 50 of gestation

Updated:12/3/12

Sow - Do after day 111 of gestation

PGF2α (Lutalyse 10 mg/IM) parturition in 29-48 hours.

Note that this is less than 3 Days from normal parturition

Close synchrony - Lutalyse at 8 AM followed by oxytocin 40 IU 24 hours later. Sows farrow between 8 AM and 5 PM (32 hours from start)

Piglets should be born within 1 to 8 (average 1-4) hours with 15 minute intervals between piglets - May give oxytocin in last few piglets to decrease stillborn numbers in large litters or after extended delivery interval

Its is important to give PGF2α no earlier than Day 111. If given on Day 110 will cause stillborn piglets ( too immature to survive)

9!

Updated:12/3/12

Mare - Do after day 320 of gestation

Oxytocin (20-60 I.U.) close to term !!!

Takes less than 1 hour! Placenta expelled in < 1 hour

Make sure of the following before inducing foaling:

1. Udder is enlarged with presence of colostrum 2. There is relaxation of the perineal region 3. Cervical relaxation (can insert 1 to 2 fingers)

Usually induce for only two reasons: 1. Demonstration 2. Prolonged gestation In normal pregnancy, mare can control time of day for foaling through her release of oxytocin. Inject oxytocin give no choice of time.