Why is maternal recognition of pregnancy important?
It prevents regression, or luteolysis, of the corpus luteum, which produces progesterone during the luteal phase of the oestrus cycle.
Progesterone, through negative feedback to the hypothalamus and anterior pituitary, inhibits the production of GnRH & gonadotrophins FSH & LH, which would otherwise lead to another unwanted oestrus cycle & ovulation during pregnancy.
Aside from preventing the start of another oestrus cycle & ovulation through negative feedback, what other functions are provided by progesterone to the pregnant female?
- prepares the uterus to receive the conceptus by causing the endometrium to thicken & to produce nourishment in the form of “uterine milk” for the ovum as it travels through the oviduct
- depresses uterine contractions during pregnancy
- stimulates growth of mammary glands while suppressing secretion of milk
- promotes formation of non-penetratable cervical mucous
- anti-oestrogenic - inhibits oestrogen-synthesis
- anti-androgenic - inhibits androgen-synthesis
- mild effect on sodium loss via distal convoluted tubule of kidney
The luteal phase is longer than the follicular phase in domestic animals, because the corpus luteum regresses in the process of luteolysis, caused by the eicanosoid PGF2a, synthesized in the uterus.
PGF2a is produced only when enough oxytocin, produced in all animals except the mare by the CL itself, binds to oxytocin receptors in the uterus. The uterus doesn't always express OTRs - they're only expressed "in time" for the luteal period.
When the CL regresses, P4 levels drop off, removing the negative feedback to the hypothalamic-pituitary-gonadal axis for secretion of GnRH, gonadotrophin and androgen/oestrogen synthesis & secretion that result in a new oestrus cycle & ovulation.
During pregnancy, it is critical that the CL continue to produce P4 during the gestation period. In only the rare case of the bitch, the natural luteal period of 75 days is longer than the gestation period of about 60 days, so the CL continues to make P4 without the need for maternal recognition.
Most other animals have a mismatch between the lifespan of the CL & their gestation period, so another mechanism for maternal recognition is needed so that the CL's lifespan -- and P4 production -- can be extended.
What are the lifespans of the CL (luteal period, non-pregnant) in ewes, cows, sows, mares, queens, bitches & women, and how do they compare with the typical gestation periods?
CL lifespan = 14 days (13-15)
Gestation = 147 days (~5 months)
CL lifespan = 18 days (17-19)
Gestation = 282 days
CL lifespan = 16 days (15-17)
Gestation = 115 days (just under 4 months)
CL lifespan = 15 days (14-16)
Gestation = 330 days (11 months)
CL lifespan = 40-45 days
Gestation = ~63 days
CL lifespan = 60-75 days
Gestation = ~63 days
CL lifespan = 14 days (12-15)
Gestation = 280 days
What is the pregnancy-recognition factor in the ewe, when does it kick in, and how does it work?
The ewe's natural luteal period is only about 14 days, while its gestation period is 147-150 days, so it needs to extend the life of its CL to produce progesterone for about 30 days, until the Placenta takes over P4 production by ~Day 45.
The pregnancy-recogition factor is ovine interferon-tau, expressed by the conceptus from Days 13/14 of oestrus cycle.
o-IFNtau prevents uterine-endometrium acquisition of oxytocin receptors (OTR) during pregnancy
∴ oxytocin continues to be secreted by CL, but can’t bind to anything → no PGF2α → CL retained (also promotes endometrial secretions)
Does NOT enhance P4 production ∴ NOT luteotrophic
What is the pregnancy-recognition factor in the cow, when does it kick in, and how does it work?
The natural luteal period for a cow is about 18 days, while its gestation is 282 days, so the life of its CL must be extended for sustained P4 production. Unlike the ewe, the cow is reliant on the CL for P4 production throughout pregnancy as the placenta doesn't take over P4 production as early if at all.
The pregnancy-recognition factor in cows is bovine interferon-tau, which is expressed by the conceptus by about Day 14 or 15 of oestrus.
bIFN-tau, like oIFN-tau, prevents the expression of oxytocin receptors (OTR) in the uterine endometrium. So while the CL continues to produce oxytocin, it can't bind to any OTR, so PGF2a will not be made by the uterus, and thus the CL will not undergo PGF2a-induced luteolysis. P4 continues to be produced.
What is the pregnancy-recognition factor in the sow, when does it kick in, and how does it work?
The sow's natural luteal phase is about 16 days long, and its gestation is 115 days, so the life of the CL & P4 production must be extended to maintain pregnancy.
The pregnancy-recognition factor in sows is oestradiol (E2), produced by the conceptus (blastocyst) at about Days 11/12 of the oestrus cycle.
Oxytocin continues to be produced by CL & the posterior pituitary, & lots of PGF2α also produced by the uterus as the oxytocin binds to OTRs, but:
E2 reduces overall secretion of PGF2α by re-routing it:
- reduces amount of PGF2α to be secreted into circulation (endocrine), diverting out to uterine lumen (exocrine), where it’s destroyed
- transfers PGF2α in venous blood & lymph back to uterus, where it's destroyed
- ability of uterine vein & artery to accumulate PGF2α
- E2 also stimulates myometrial contractions to enable proper spacing of embryos along uterine horn (big litters need to be well-spaced)
- E2 is luteotrophic & anti-luteolytic:
- promotes PGE2 secretion by uterus → binds to e-prostanoid receptors (EP) on CL → more P4 production
- causes ↑ LH receptors on CL
What is the pregnancy-recognition factor in the mare, when does it kick in, and how does it work?
The mare's natural luteal period is about 15 days, while gestation is 330. eCG (PMSG) is secreted from about Days 35-40 via endometrial cups, which cause secondary ovulations & thus secondary CLs that produce P4 until about Day 100, when placenta takes over P4 production. So initial CL must be extended for about 30-35 days.
The pregnancy-recognition factor in mares is unknown, but whatever it is, it is expressed from Days 12-14 of the oestrus cycle. It might be a combination of three proteins including oestradiol, but it is NOT eCG.
Down-regulation of endometrial OTRs occurs, possibly due to oestradiol (E2) as in pigs, since mares produce a lot of E2 from Day 10 of fertilisation, but it’s unproven. NB oxytocin is made by the uterus, not the CL, in the mare.
Unknown signal distributed by the spherical embryo as it moves “round & round” uterine lumen from one uterine horn to another, 12-14 times a day, until ~Day 17 after ovulation, when it “fixes” in position due possibly to increased uterine tone. Oddly, the embyro’s “transuterine mobility” is enabled by PGF2α, which is secreted by the embryo at about Day 10 (it also secretes PGE2).
The unknown signal prevents production of prostaglandins by uterus.
What is the pregnancy-recognition factor in the queen, when does it kick in, and how does it work?
The luteal phase of the cat is about 40-45 days, but the gestation period is 63 days, so an extension of the life of the CL for P4 production must occur to sustain pregnancy.
The maternal-recognition of pregnancy factor is unknown, but probably prolactin.
What is the pregnancy-recognition factor in the woman, when does it kick in, and how does it work?
The woman's natural luteal period is 14 days, while gestation is 280 days. The placenta takes over P4 production on Day 60 of oestrus cycle, so to life of the CL must be extended by 46 days.
The pregnancy-recognition factor in women is hCG (human chorionic gonadotropin), which is expressed by the conceptus from Days 7-12 of the oestrus cycle.
hCG is a more-potent form of LH with a longer half-life; it binds to LH receptors on the CL.
Detected by Day 9 after ovulation, but actions on CL unknown.