W5L2 Tues Maternal Recognition of Pregnancy Flashcards
what is MRP and important factor about it
Physiological process through which the conceptus modulates maternal function to preserve pregnancy, notably prolongation of the life span of the CL and of progesterone secretion.
-Balance between positive luteotrophic and negative luteolytic factors (species specific)
* Timing and strength of signal key- early embryo loss
Different type of placentation
§ Invasive placentation: the placenta invade deeply into the maternal tissues .mouse, rat, rabbit, human
§ Non-invasive placentation: the placenta remains relatively superficial and does not invade deeply into the maternal tissues. sheep, pig, cow, horse
Embryo Develoment stages and timing difference between invasive and non invasive species
§ Cleavage to 4 cells: b/w 1-3 days after ovulation
§ Major burst of transcription: b/w 2-cell to 16-cell stage
Ø Continuous activation of embryo genome
Ø Previously embryo used maternal transcripts
§ Blastocyst formation: day 3-4 (invasive), day 6-8 (non-invasive)
§ Time of attachment: day 4-7 (invasive), day 15-40 (non-invasive)
§ Luteal regression if mating infertile day 10-12 (invasive), day 16-20 (non-invasive)
Human, primates ovarian cycle
distinct follicular + luteal phases
Cow and sheep ovarian cycle
§ Cows/sheep: waves of follicular growth during luteal phase
Ø High progesterone = follicle atresia
Ø Low progesterone = ovulation
Mouse and rat ovulation
§ Mouse/rat: normal oestrous cycle ~4 days, pregnancy 21-22 days
Ø Pseudopregnancy: cervical stimulation causes release of prolactin (luteotrophic so CL develops + secretes progesterone for 11-14 days)
Cat and rabbit ovulation
§ Cat/rabbit: induced ovulators
Ø Pseudopregnancy: mating induces LH surge + ovulation, CL declines at ~21 days if not pregnant (65 day gestation)
Experiment on sheep to show Progesterone is needed to maintain pregnancy
§ Sheep: 15-16 day cycle, 150 day gestation
Ø Hypophysectomy (pituitary): terminates pregnancy before day 50, after day 50 placenta maintains pregnancy + releases LH (unaffected)
Ø Ovariectomy (CL): terminates pregnancy before day 55, after day 55 placenta produces progesterone (unaffected)
Experiment on goat to show Progesterone is needed to maintain pregnancy
§ Goat: 21 day cycle, 150 day gestation
Ø Hypophysectomy + ovariectomy terminates pregnancy
Ø No transfer of primary source of progesterone to placenta
Ø Progesterone maintained by pituitary + CL throughout gestation
source of Progesterone to Maintain Pregnancy
§ LH from pituitary stimulates CL to produce progesterone which acts on uterine endometrium
§ Conceptus produces placental gonadotrophins which act on CL to maintain progesterone production
§ In some species, placenta becomes primary producer of progesterone + thus sustains pregnancy
Ø In other species, CL must always be present
Luteal Rescue process and confirmation test in human
§ No embryo present → no embryonic signal → passive luteolysis (PG + oxytocin)
§ Chorionic gonadotrophin (CG) is a glycoprotein related to LH + FSH (mostly LH-like activity)
Ø Produced by placental tissues (syncytiotrophoblasts) from 6-7 days after fertilisation
Ø Prevents CL regression
§ Injection of CG extends luteal function in non-pregnant females (↑progesterone)
§ Antibodies to CG in early pregnancy prevents luteal rescue (↓progesterone) + pregnancy fails
Hormones in human pregnancy
§ Progesterone: produced by CL + then placenta from ~6 weeks
§ Oestrogens made in placenta include oestriol > oestrone > oestradiol
Ø Foetus produces weak androgen precursors from adrenal glands/liver
Ø Oestrogens can act on foetus, so foetal adrenals/liver add sulphur groups (sulphonate) to inactivate oestrogens
Ø Placenta cleaves the sulphur groups to activate oestrogen for use
Ø Important in blood flow/angiogenesis of BVs, invasion, placentation, fluid regulation for healthy pregnancy
§ hCG: initial surge at ~25-100 days to keep CL alive
§ human Placental lactogen (hPL): similar to growth hormone, ensures exponential growth of foetus in late pregnancy
MRP in Other Species
- Active luteolysis: action of luteolytic agent PGF2a, overcomes anti-luteolytic benefits of LH
- Instead of CG (prevents CL regression) in primates: IFN-τ (ruminants), oestrogen (pigs), oestrogen/prostaglandin (horse/other species)
Early embryo development in cow
zona hatching ~day 8-9
→ trophectoderm proliferates
→ adhesion ~day 18 (tape-worm shape)
Ø Trophectoderm produces IFN-τ to maintain CL
Luteolysis mechanism in cow
↓progesterone (downregulated receptor) + ↑oestrogen due to LH/FSH pulses stimulating ovaries
Ø ↑oestrogen acts on hypothalamus which induces oxytocin release from PP + ↑oxytocin receptors in uterine endometrium
Ø Binding of oxytocin to endometrial OTR produces PGF2a which is transferred to CL via counter-current transfer
Ø PGF2a initiates luteolysis + triggers release of supplemental oxytocin from CL (= supplemental PGF2a released from circulation)
§ Luteolysis: PGF2a synthesis in uterus day 11-16 → uterine veins → counter-current transfer from vein to artery → PGF2α to ovary → PGF2α induces OT release + luteolysis → OT from CL stimulates PGF2α synthesis in uterus
§ Pregnancy: IFN-τ from blastocyst suppresses ↑OTR in endometrium + thus blocks PG synthesis