lecture 15: maternal recogntion of pregnancy Flashcards
1
Q
What is maternal recognition of pregnancy?
A
- coined by RV Short in 1969
- balance between positive luteotrophic and negative luteolytic factors (species specific)
- timing and strength of signal key – early embryo loss
- MRP: 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
2
Q
What is the zygote?
A
- fertilised/activated ovum that is now diploid
3
Q
What is the conceptus?
A
- any stage of development that represents the full product of conception, i.e. the embryo/foetus and its associated extraembryonic tissues (placenta)
4
Q
What is the embryo?
A
- strictly, the embryo proper develops into the foetus and excludes the extraembryonic tissues. However, in common usage, embryo is often used to refer to the whole early conceptus.
5
Q
What is the blastocyst?
A
- stage of embryonic development at which the embryo (strictly conceptus) has formed a cavity, at which in most species has differentiated into two cell lineages: ICM → embryo proper; trophoblast → contributes to placenta
- NB: trophectoderm = the earliest tissue of the trophoblast lineage
6
Q
What is a foetus?
A
- embryonic stage after the start of organ development
7
Q
What is the time (in days) after ovulation at which various developmental and maternal events occur?
A
invasive
- mouse
- cleavage to four cells: 1.2 - 2
- major burst of transcription: 2-cell
- conceptus enters uterus: 3
- formation of blastocyst: 3
- time of attachment: 2.5
- luteal regression time if mating infertile: 10-12
- duration of pregnancy: 19-20
- rat
- cleavage to four cells: 2-3
- major burst of transcription: 2-cell
- conceptus enters uterus: 3
- formation of blastocyst: 2.5
- time of attachment: 4.5 - 5.5
- luteal regression time if mating infertile: 10-12
- duration of pregnancy: 21-22
- rabbit
- cleavage to four cells: 1-1.5
- major burst of transcription: 8-16-cell
- conceptus enters uterus: 3.5
- formation of blastocyst: 3.5
- time of attachment: 7-8
- luteal regression time if mating infertile: 12
- duration of pregnancy: 28-31
- human
- cleavage to four cells: 2
- major burst of transcription: 4-8-cell
- conceptus enters uterus: 3.5
- formation of blastocyst: 4.5
- time of attachment: 7-9
- luteal regression time if mating infertile: 12-14
- duration of pregnancy: 270-290
non-invasive
- sheep
- cleavage to four cells: 4
- major burst of transcription: 8-16-cell
- conceptus enters uterus: 2-3
- formation of blastocyst: 6-7
- time of attachment: 15-16
- luteal regression time if mating infertile: 16-18
- duration of pregnancy: 144-152
- pig
- cleavage to four cells: 1-3
- major burst of transcription: 4-cell
- conceptus enters uterus: 2
- formation of blastocyst: 5-6
- time of attachment: 18
- luteal regression time if mating infertile: 16-18
- duration of pregnancy:
112-115
- cow
- cleavage to four cells: 2-3
- major burst of transcription: 8-16-cell
- conceptus enters uterus: 3-4
- formation of blastocyst: 7-8
- time of attachment: 30-45
- luteal regression time if mating infertile: 18-20
- duration of pregnancy:
277-290
- horse
- cleavage to four cells: 1.5 - 2
- major burst of transcription: ?
- conceptus enters uterus: 5 - 6
- formation of blastocyst: 6
- time of attachment: 30 - 40
- luteal regression time if mating infertile: 20-21
- duration of pregnancy:
330 - 345
8
Q
What are different kinds of ovarian cycles?
A
- human and other primates
- cows, sheep
- waves of follicular growth during luteal phase
- mouse, rat
- truncated luteal phase
- pseudopregnancy
- cat, rabbit
- induced ovulation
- pseudopregnancy
9
Q
What is pseudopregnancy?
A
- seen in many species
- rat and mice
- in normal oestrous cycle is relatively short (~4 days)
- cervical stimulation at mating causes reflex release of prolactin
- prolactin is luteotrophic so CL develops and secretes progesterone for 11-14 days (vs pregnancy 21-22 days)
- cats
- induced ovulators
- mating → reflex LH surge and ovulation
- if not pregnant, CL starts to decline after about 21 days (vs gestation 65 days)
10
Q
Is progesterone essential to maintain pregnancy?
A
- yes
- generally
- not all species are the same
- sheep
- hypophysectomy terminates pregnancy up until day 50
- waiting until after this has no effect on the pregnancy
- ovariectomy terminates pregnancy up until day 55
- after this time the placenta has taken over and is capable of producing the right hormones etc to support the pregnancy independently
- pregnancy usually ~ 150 days
- hypophysectomy terminates pregnancy up until day 50
- goat
- also pregnancy ~ 150 days
- hypohysectomy and ovariectomy terminate pregnancy all the way up to term
- placenta unable to take on characteristics well enough to support the pregnancy without those other organs
- species differ in how they may utilise maternal and/or foetal/placental progesteron production
- LH support from pituitary
- supports corpa lutea and production of progesterone acting on the uterus itself
- after the early stages of pregnancy the placenta then takes on a role and itself is releasing gonadotrophins
- these are able to maintain the corpus luteum
- in some species we don’t actually need LH from pituitary
- placental progesterone is also there to help in terms of the production and maintenance of the pregnancy itself, not just CL, functions both within the uterus and the ovary
11
Q
What is luteal rescue in primates?
A
- passive luteolysis
- due to failure of embryonic signal
- endogenous factors in CL (PG and oxytocin)
- fertile coitus → embryo releases CG which rescues the corpus luteum → keeps producing progesterone → pregnancy maintained
- chorionic gonadotrophin
- glycoprotein related to LH and FSH
- mostly LH like activity
- produced by placental tissues – syncytiotrophoblast
- production from about 6-7 days after fertilisation
- prevents CL regression
12
Q
What are some of the hormones in human pregnancy?
A
- placental production of:
- progesterone (absolute requirement) - CL/Placenta
- Oestrogens
- foetus, role of foetal adrenal/liver
- change in type of oestrogen, species
- oestriol >> oestrone > oestradiol (importance, in general)
- importance for receptivity, fluid balance etc
- required but not absolute requirement
- placenta doesn’t have all of the enzymes/substrates to produce all of the oestrogens
- produced by foetus → bound to sulphates to prevent exposure (important for male foetus)
- hCG (urinary excretion → home pregnancy test)
- produced around blastocyst stage
- massive surge
- drops to just above basal
- only required in the inital phases up to about day 100, where the placenta is able to take over
- placental lactogen (hPL)
- produced around the same time as the placenta formation and slowly increases
- nutrient partitioning to the foetus
- particular w/ IGFs and how they mediate that in the foetus
- prolactin
- in the placenta it’s all about solutes, electrolytes and water balance
- used as endocrine markers of foetal and placental health
13
Q
What is the role of CG?
A
- maintains the CL
- injection of CG extends luteal function in non-pregnant females
- blocking CG action in early pregnancy prevents luteal rescue, and pregnancy fails
14
Q
What is MRP in other species?
A
- active luteolysis
- action of luteolytic agent (PGF2α)
- overcomes the anti-luteolytic benefits of LH
- most mammals – cow/sheep etc
- signals in other species
- ruminants = IFN-τ
- pigs = oestrogen
- other species = ?oestrogen/PG
- different species have evolved to use different tools
15
Q
What is seen in the ewe and the cow for MRP?
A
- non-pregnant
- oestrus - LH surge
- prostaglandin pulsatility occurs → luteolysis → cycle occurs again
- pregnant
- prostaglandin F2 alpha is suppressed
16
Q
What is early embryo development in cows?
A
- fertilisation occurs in the oviduct
- day 4-5 enters uterus
- blastocyst
- day 9 - blastocyst gets rid of its zona pellucida
- the outer cells start rapidly expanding - a couple of mm a day
- turn into what looks like a very large tape worm
- embryo proper/ICM does not grow at this point
17
Q
What is luteolysis in the cow?
A
- ovarian artery coils around uterine veins
- around day 11-16 PGF2alpha synthesis in uterus transported by veins
- stimulated by oxytocin receptors
- PGF in uterine drainage
- counter current system → transfer from vein to artery
- PG carried to ovary
- allows it to have direct action on the ovary instead of being circulated around the body
- PGF induces OT release from large luteal cells and luteolysis
- OT from CL stimulates PGF 2a synthesis in uterus
- positive reinforcement
18
Q
How is luteolysis blocked in the cow?
A
- interferon-tau from the blastocyst suppresses OTR increase and thus PG synthesis
- stops PGF synthesis and release → skews production towards PGE which is beneficial in maintaining the CL
20
Q
What is MRP in pigs?
A
- luteolysis in cyclic pigs via oxytocin and increased uterine PGF2alpha
- requires at least one embryo in each uterine horn
- rescue at day 11-13 coincident with blastocyst expansion
- not as large as in cow or sheep
- expanding blastocyst makes oestrogens
- treatment of non-pregnant sows with oestrogen, either systemically or intra-uterine, at this time extends luteal function
- oestrogen from the conceptus has BOTH
- anti-luteolytic actions
- diverts PGF2a to exocrine secretion (in lumen), aided by prolactin
- luteotrophic actions
- produces PGE2, → LHR
- anti-luteolytic actions
- conceptus also produces IFN-gamma and delta
- don’t know what they do
- not necessarily essential
- cyclic
- endocrine
- PGF2a secreted from uterus into uterine vein at day 11-16
- PGF2a induces luteolysis
- pregnancy
- exocrine
- PGF2a secreted from uterus into uterine lumen at day 11-16
- blastocyst oestrogens redirect direction of PGF2a secretion
- also increase PGE2 secretion (PGE2 luteotrophic)
- blastocyst also makes a nocel interferons - angiogenic/immune effects?
