W5L2 Tues Maternal Recognition of Pregnancy

Question 1

what is MRP and important factor about it

Answer 1

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

Question 2

Different type of placentation

Answer 2

§ 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

Question 3

Embryo Develoment stages and timing difference between invasive and non invasive species

Answer 3

§ 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)

Question 4

Human, primates ovarian cycle

Answer 4

distinct follicular + luteal phases

Question 5

Cow and sheep ovarian cycle

Answer 5

§ Cows/sheep: waves of follicular growth during luteal phase
Ø High progesterone = follicle atresia
Ø Low progesterone = ovulation

Question 6

Mouse and rat ovulation

Answer 6

§ 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)

Question 7

Cat and rabbit ovulation

Answer 7

§ Cat/rabbit: induced ovulators
Ø Pseudopregnancy: mating induces LH surge + ovulation, CL declines at ~21 days if not pregnant (65 day gestation)

Question 8

Experiment on sheep to show Progesterone is needed to maintain pregnancy

Answer 8

§ 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)

Question 9

Experiment on goat to show Progesterone is needed to maintain pregnancy

Answer 9

§ 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

Question 10

source of Progesterone to Maintain Pregnancy

Answer 10

§ 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

Question 11

Luteal Rescue process and confirmation test in human

Answer 11

§ 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

Question 12

Hormones in human pregnancy

Answer 12

§ 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

Question 13

MRP in Other Species

Answer 13

• 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)

Question 14

Early embryo development in cow

Answer 14

zona hatching ~day 8-9
→ trophectoderm proliferates
→ adhesion ~day 18 (tape-worm shape)
Ø Trophectoderm produces IFN-τ to maintain CL

Question 15

Luteolysis mechanism in cow

Answer 15

↓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

Question 16

MRP in Ruminants and the role of IFN-t

Answer 16

§ Luteolysis via pituitary/CL oxytocin + uterine PGF2a
§ Production of IFN-τ from mononuclear trophoblast cells of conceptus from blastocyst stage
Ø Blocks uterine oestrogen + oxytocin receptor upregulation
Ø Promotes PGE2 production (luteotrophic, maintains CL)
Ø Stimulates endometrial gene expression (with progesterone) to prepare for pregnancy
§ Free floating conceptus for 18 days relying on uterine secretions
§ Acts via IFNAR1 + 2 via multiple secondary messenger pathways (JAK-STAT)

Question 17

MRP in Pigs

Answer 17

§ Luteolysis via oxytocin + ↑uterine PGF2a
§ MRP requires at least 1 embryo in each uterine horn
§ CL rescue at day 11-13 coincident with blastocyst expansion + production of oestrogens
Ø Treatment of non-pregnant sows with oestrogen extends luteal function
§ Oestrogen from conceptus has 2 functions:
Ø Anti-luteolytic actions: diverts PGF2a to exocrine secretion (uterine lumen) aided by prolactin + degraded
Ø Luteotrophic actions: produces PGE2 which sustains LH support by upregulating LHR in CL which maintains CL
§ Conceptus also produces IFN-γ + δ (type 1 interferons)

Question 18

Hormones in the sow

Answer 18

§ Cyclic sow (endocrine): PGF2a secreted form uterus into uterine vein (day 11-16) → PGF2a induces luteolysis
§ Pregnant sow (exocrine): PGF2a secreted from uterine lumen (day 11-16) → blastocyst oestrogens redirect direction of PGF2a secretion + ↑PGE2 secretion (luteotrophic)

Question 19

MRP in Horses

Answer 19

§ Luteolysis via uterine PGF2a (produced by conceptus)
§ Conceptus migrates 12-14 times a day along uterine horn + secretes PGF2a
Ø Anti-luteolytic or luteolytic signal is unknown
§ Expanding blastocyst makes oestrogens, principally oestrone (equilin, equilenin) + IFN-δ
§ PMSG/eCG produced by conceptus from day 40 causes a secondary ovulation
Ø Production of secondary CL until day 140 = more progesterone (DHP)
§ Foetal androgens (DHA sulphate) used by placenta come from foetal gonads rather than adrenals gland

Question 20

MRP in Camelids

Answer 20

§ Seasonal breeder, induced ovulator
§ Involves ↑PGF2a but anti-luteolytic signal unknown
§ CL only present for 8-9 days, left horn implantation only