Lecture 8 - The Challenges of Viviparity/Pregnancy

Question 1

Challenges of viviparity/pregnancy

Answer 1

• embryonic, feta, and maternal challenges
• embryonic and fetal growth
• the placenta as a barrier
  
  • placenta to stop flow between maternal and fetal circulation, but works to let some things in and some things out
• placental transport mechanisms

Question 2

Embryo vs Fetus

Answer 2

• when body plan laid down completely it’s a fetus
• embryo up until that
• about 6 weeks that’s long after implantation - so implantation in the embryo phase

Question 3

Challenges faced by the embryo

Answer 3

• nutrition
• body plan
• implantation

Question 4

Challenges faced by a fetus

Answer 4

• big enough to survive
• develop enough to survive

Question 5

Challenges for an embryo/fetus

Answer 5

• preventing the demise of the corpus luterum (luteolysis)
  
  • stops producing progesterone → endometrium shed
  • true for an embryo - too late for a fetus
  • need an endometrium to implant into
• growth and development
  
  • for both embryo and fetus
• nutrition
  
  • if you’re being nourished, with calories also need gas exchange
• gaseous exchange
  
  • won’t respire at all if don’t have oxygen to respire the calories
  • have CO₂ to get rid of it
• elimintation of waste (toxic?)
  
  • eg making urea in amniotic fluid
  • break down hemoglobin to iron → bilirubin that’s toxic

Question 6

Preventing luteolysis

Answer 6

• defined as the maternal recognition of pregnancy
• most mammals, require an early embryo to produve (or to stimulate the production) of either
  
  • a leutotrophin - stops the corpus luteum shrinking
  • an anti-luteolysin - luteolysis kills corpus luteum so need something to prevent this (negative of negative)

Question 7

Maternal recognition of pregnancy in primates

chorionic gonadotropin

Answer 7

• pre-implantation trophoblast synthesizes and secretes
  
  • human chorionic gonadoptrophin (hCG)
  • monkey chorionic gonadotropin (mCG)
• very similar molecular structure to LH - identical α-GSU but C-terminal extension to CGβ
  
  • α subunit of LH and CG are identical
    
    • active part of the molecule
  • hGC compared to human LH has about another 24 amino acids of the C-terminal of the β-subunit
    
    • gonadotrophins are glycoproteins
    • so if 24 amino acids longer how to make it bigger, longer half-life, stay in circulation and not degraded?
    • if introduce more glycosylation = more sugar over the moleculle and last longer in circulation so more N and O-linked glycosylation sites
• hCG and mCG activate the same G protein-coupled receptor as LH
• the corpus luteum is dependent on LH - one of the reasons it dies is becuase it doesn’t get enough LH support so when embryo formed have to keep the CL going (stimulate that same LH receptor - LHCGR - LH and corionic gonadotorphic receptor because it will bind both (identical α-subunit)

Question 8

Maternal recognition of pregnanty in primates

chorionic gonadotrophin - continued

Answer 8

• hCG/mCG activates the same GPCR as LH
  
  • LHCGR
• up-regulates the same genes as LH, required for P₄ (and E₂) synthesis by luteal cells
• corpus luteum depends on LH
• need to stimulate the same LH receptor - that’s why it’s called LHCGR
• increase output of steroid from CL

Question 9

Maternal recognition of pregnancy in horses

chorionic gonadotrophin

Answer 9

• trophoblast in the endometrial cups synthesizes and secretes equine chorionic gonadotrophin (eCG)
  
  • horse has diffuse placenta (no discoid chorion) so trophoblast sits in endometrial cups
  • trophoblast makes eCG
• has both LH and FSH activity
• activaton of LHCGR and FSHR stimulates development and ovulation of more follicles
  
  • where primates mimic LH, this one mimics FSH as well (better at FSH even, than LH)
  • animal already pregnant but has to make more ovulations happen
    
    • forms new corpora lutea
    • in primates stimulate the existinc CL hormone to produce progesterone
    • in the case of the horse - and elephants - have accessory ovulations to give new CL to contribute progesterone
    • the ovulations have nothing to do with conception (animal already pregnant) just to put progesterone in for existing embryo

Question 10

Maternal recognition of pregnancy in ruminants

Answer 10

• in sheep and cattle, luteolysis is triggered by PGF2α from the uterine endometrium
• endometrial PG synthesis (epithelial and glandular cells) stimulated (via GPCR) by oxytocin (OT) from the corpus luteum
• interferon-τ represses epxression of OT receptors (OTR)

luteolysis is different

• in sheep and cattle the death of the CL doesn’t happen just because LH runs out but active destruction of the CL by PGF2α from the uterus
• if the thing that kills the CL comes form the uterus how can you establish that surgically?
  
  • to keep corpus luteum alive - remove the uterus
  • hysterectimize a ewe = CL carries on forever because something coming from the uterus
• the CL in cows and sheep makes oxytocin protien that goes tot he endometrium to stimulate thee ndometrium to make PGF2α which kills the CL
  
  • explains the clock for the 2 weeks that the CL will survive form
  • CL makes progesterone, at some point makes oxytocin which triggers its death by a dialogue with the uterus
• in the case of pregnancy, an embryonic lamb or calf will makei nterferon-τ which switches off the oxytocin receptor (OTR)
  
  • if no oxytocin receptor = broken the dialogue between the ovary and the uterus
  • the uterus doesn’t make luteolytic PGF2α and the CL survives
• OTR - no luteolytic PGF2α signal
  
  • uterus doesn’t make this and the CL dies
• difference between producing something to stimulate the CL and something that prevents the death of the CL
  
  • but are the embryos top priority because if the CL dies and progesterone declines = endometrium shed, embryo with it