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ANIMAL PRODUCTION - Reproduction > 16 – Parturition > Flashcards

16 – Parturition Flashcards

1
Q

Parturition definition

A
  • Act of giving birth to young
  • Ex. foaling, calving, farrowing, lambing, whelping, queening
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2
Q

Key players involved in parturition

A
  • Fetus (fetal hypothalamic-pituitary-adrenal (HPA) axis
  • Fetoplacental unit
  • Uterine musculature
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3
Q

Fetal HPA provides a major input on

A
  • Length of gestation
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4
Q

Fetoplacental unit

A
  • Fetal HPA and gonads
  • Placenta
  • Endometrium
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5
Q

Uterine musculature (myometrium)

A
  • Biochemical ripening of the cervix
  • Transition from quiescent to powerfully coordinated contractile muscle
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6
Q

Sheep model of parturition

A
  • Factors that initiate birth and terminate pregnancy are likely MULTIFACTORIAL
  • Major animal model used
    o Mechanism not well understood in pig, horse, dog, cat
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7
Q

Experiments in 1960s based on natural occurrences

A
  • Herd of cows had prolonged pregnancy and a heritable disorder resulting in very small pituitaries and adrenal glands
  • Pregnant sheep in Nevada mountains had no parturition or delivered at 200d (vs. 147d)=displacement or absence of pituitary
    o Ingested a plant (Corn Lilly)=has teratogens (alkyloids)=cause malformations OF or WITHIN an embryo
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8
Q

Activation of fetal HPA likely result of

A
  • Development of critical synapses in hypothalamus
  • Hypothalamus responding to placental hormones
  • Fetal stressors (ex. BP, glucose)
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9
Q

Increased cortisol concentrations in ewe within last 15-20 days of gestation

A
  • Increased cortisol production from fetal adrenals that increase in size and response to ACTH
  • **Fetal plasma ACTH levels rise in response to increased hypothalamic production of arginine vasopressin and CRH
    o CRH can be produced by placenta
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10
Q

2 ‘mechanisms’ of how increased fetal cortisol has implications for intrauterine prostaglandin synthesis

A

*cyclic fatty-acid hormone like compounds (starting block=AA)
- Estrogen-independent
- Estrogen-dependent

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11
Q

Breakdown of AA by

A
  • COX2: PGHS2(PG synthetase)
    o Goes into PGF2 or PGE2
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12
Q

Estrogen-independent prostaglandin synthesis

A
  • Cortisol produced and stimulates placental trophoblast (PGHS 2) to produce PGE2
  • PGE2 stimulates P450 enzyme
  • Pregnenolone is converted into different steroids
    o *DHEA: dehydroepiandrosterone
    o Ultimately go into estrogen and get estrogen-dependent PG synthesis
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13
Q

Estrogen-dependent prostaglandin synthesis

A
  • Once estrogen produced by placenta (estrogen-independent PG synthesis) it will induce endometrium (maternal side): PGHS2
  • Production of PGF2 produced=uterine contractility
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14
Q

Feto-placental unit (pregnenolone ‘different’ pathways)

A
  • Pregnenolone being used to get steroid hormones
  • *shifting it from being produced to get progesterone to now get estradiol!
  • *shift drives the drop in progesterone and increase in estradiol
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15
Q

What is progesterone highly produced by in ruminants?

A
  • CL
    o So PGF2alpha may also luteolysis
    o Also get PGF2alph from estrogen-dependent PG synthesis
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16
Q

Estradiol production stimulates

A
  • Production of CAPS (contraction associated proteins) including
    o Gap junction proteins
    o Oxytocin receptors
    o Prostaglandin receptors
    o Calcium channels
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17
Q

Estrogens also stimulate and promote

A
  • Stimulate cervical and vaginal mucous secretion for lubrication to aid birth
  • Promotes cervical ripening
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18
Q

Prostaglandin effects on myometrium and cervix

A
  • Depends on which receptors it binds to (PGE2 and PGF2alpha)
    o Slightly different pathways with different consequences
  • *different receptors in myometrium and cervix for both PGE2 and PGF2alpha)
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19
Q

Receptors that cause increased myometrial contractility

A
  • PGE2: EP1 and EP3
  • PGF2alpha: FP
20
Q

Ferguson’s reflex

A
  • Uterine contractions of parturition forces fetus toward cervix and vagina
  • Stimulate pressure sensitive neurons in cervix which synapse with neurons in hypothalamus
    o *leads to increased oxytocin secretion and cycle of greater contractions with greater pressure on cervix (+ FEEDBACK!)
21
Q

Oxytocin effects on uterus (myometrium and endometrium)

A
  1. Binds to myometrium receptors and stimulates myometrium to increase intracellular Ca levels=binding of actin-myosin=smooth muscle contraction
  2. Bind to receptors in endometrium=stimulate PGF2alpha synthesis and secretion=even more uterine contractions
22
Q

Myometrial contractile activation

A
  • Needs to be electrically and metabolically coupled
    o Increase in gap junction production and communication just prior to and during labour
  • *genetic studies how removal of Cx43 gap junction gene IMPAIRS parturition
23
Q

Fetal growth-induced uterine distension

A
  • Growth distends uterus and stimulates expression of CAPs that aid parturition
    o Cx43 (GJ protein)
    o Oxytocin receptors
    o Prostaglandin receptors
  • *primes myometrial cells to be properly adhered to one another and promote COORDINTED contractions
24
Q

Sow parturition

A
  • Unclear of fetal participation
  • Estrogens probably not involved in stimulating release of PGs
  • Exogenous estrogens do NOT induce farrowing
25
Q

Mare parturition

A
  • Progesterone levels in last 3rd are very LOW
    o Progestogens are responsible for uterine quiescence
  • Progestogens in maternal plasma drop with increasing fetal cortisol levels
  • Mare uses fetal gonads to a larger extent to supply androgens (DHEA) for estrogen biosynthesis
    o NOT progesterone or pregnenolone
    o Equine placenta lacks P450 C17 hydroxylase activity
  • *fetal gonads are bigger contributor to fetoplacental unit than adrenals in equine
26
Q

Progestogens

A
  • Metabolites of P4 and pregnenolone
27
Q

Dog parturition

A
  • No fetal cortisol secretion data
  • Rapid decline in maternal P4 prior to birth with increased released of PGF2alpha from placental trophoblast (PG may not be luteolytic)
  • Maternal oxytocin levels indicate it is NOT responsible for initiating parturition
28
Q

Cat parturition

A
  • Domestic cats: PG levels in plasma unreported
  • Wild cats: indicated increases (fetal levels) toward parturition
  • Estradiol levels peak 1 week before parturition and decline markedly by labour
29
Q

Overview of impact of endocrine events on parturition

A
  • Fetal hypothalamus
    o Receive signals to become mature (stressors, axis of hypothalamus, estrogens from placenta)
  • Signals form hypothallus activate pituitary
  • Get ACTH production
  • Adrenals release steroids (ex. cortisol)
  • Cortisol improves fetal maturation (ex. lungs) and decrease in placental PG production->shift to estrogen production
    o Increased gap junctions and expressions
  • Estrogen production effect on myometrium-> release of PGF2alpha (can bind to EP4 receptors in cervix=softening) (maybe also release relaxin)
    o Effect on contractility and luteolysis of CL (species dependent)
    o Fetus towards cervix and vagina (+ abdominal straining)
    o Ferguson’s reflex (oxytocin production)
30
Q

Impact of endocrine changes on fetal maturation

A
  • Stimulate closure of ductus arteriosus and foramen ovale
  • Maturation of fetal lungs
  • Glucose homeostasis
  • Maturation of thyroid gland
31
Q

Maturation of fetal lungs (impact of endocrine changes on fetal maturation)

A
  • Production of alveolar surfactant: stimulated by fetal cortisol form adrenals
  • Resorption of fetal fluids by lungs stimulated by adrenaline from fetal adrenal glands
32
Q

Glucose homeostasis (impact of endocrine changes on fetal maturation)

A
  • Accumulation of liver glycogen stores in late gestation: stimulated by fetal cortisol
33
Q

Maturation of thyroid gland (impact of endocrine changes on fetal maturation)

A
  • THs altered to enhance biological activity
34
Q

Phases of parturition

A
  1. Quiescence (95%)
  2. Activation
  3. Stimulation
  4. Involution
35
Q

Quiescence period (phase 0)

A
  • 95% of gestation marked by myometrial quiescence and non-dilated cervix
36
Q

Activation period (phase 1)

A
  • Softening of cervix
  • Myometrium becoming prepared for contractions with increased CAPs (GJs, PG receptors) and uterine factors (PGs, E2)
37
Q

Stimulation period (phase 2)

A
  • Increased contractility
  • Large surges of PG and oxytocin release
  • Dilation of cervix
  • Delivery of fetus
38
Q

Involution (phase 3)

A
  • Afterbirth delivered
  • Uterus and cervix begin to be remodeled back to non-pregnant stage
39
Q

Why would you need to terminate a pregnancy?

A
  • Mismating
  • Twins in mares
  • Risk to dam’s health
  • *straight forward in some species (ex. pigs and goats)
40
Q

Pigs: pregnancy termination

A
  • Terminated at any stage with PGF2alpha
    o Repeated injections may be needed
41
Q

Goats: pregnancy termination

A
  • Terminated at any stage with PGF2alpha
42
Q

Cows: pregnancy termination

A
  • Terminated from 4-100d (maybe 150d?) post-ovulation with PFG2 alpha
  • After 150-270d: long-acting corticosteroids +/- PGF2alpha required
    o Due to placental contributions of progesterone
43
Q

Sheep: pregnancy termination

A
  • 4-12d: PGF2 effective
  • 12-21d: resistant, maybe due to protective effects of IFN-tau
  • Over 45d, placental progesterone production increase and predominates: progesterone antagonists OR corticosteroids would be necessary
44
Q

Cat: pregnancy termination

A
  • IM injection of estradiol cypionate within 40h of mating (inhibits tubal transport)
  • PGF2alpha can be effective to induce abortion
  • Aglepristone effective in mid-pregnancy
45
Q

Dog: pregnancy termination

A
  • Tactical use of estrogens within 5 days of mating inhibits transport of zygotes from oviduct to uterine horns
  • PGF2alpha 10-14d
  • Progesterone receptor antagonists are more effective and acceptable for termination
46
Q

Horse: pregnancy termination

A
  • 1-35d administer PGF2alpha or analogue to induce luteolysis
    o Optimally: 10-15d after mating
47
Q

Horse: TWIN pregnancy termination

A
  • Surgical removal (high risk of remaining fetus and mare)
  • Ultrasound guided injection of fetus
    o Procaine Penicillin G (PPG) into fetal thorax or abdomen (30-60% success rate)

ANIMAL PRODUCTION - Reproduction (17 decks)

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