Reproductive physiology

Question 1

Discuss role of kisspeptin in pre-ovulatory LH surge

Answer 1

+ve feedback from rising oestradiol levels (as follicles grow)
Leads to (AVPV) kisspeptin up-regulation in the pre-optic area of the hypothalamus
Increase in GnRH neurone activity
Leading ultimately to LH surge

Question 2

Describe how entry into meiosis of oocytes is controlled in fetal life

Answer 2

Control of entry into meiosis

• Acquisition of meiotic competence achieved by expression of DAZL
• Mesonephros produces retinoic acid
• Retinoic acid enters the gonad stimulating production of Stra 8
• Stra 8 enables entry into meiosis
• In contrast in male embryo, Cyp26b1 present breaks down retinoic acid

Question 3

Explain how the ovary achieves regular ovulation throughout reproductive life despite loss of follicles

Answer 3

• Steady trickle of primordial follicles activate growth and enter growing pool
• Requires sufficient quiescent and growing follicles to serve reproductive lifespan

Question 4

Discuss the role of capacitation in sperm

Answer 4

o Capacitation is the removal of glycoprotein coat and seminal proteins and alteration of sperm mitochondria
o Capacitation is required to render sperm competent to fertilize an oocyte
o The uterus aids the steps in capacitation by secreting sterol-binding albumin, lipoproteins and proteolytic and glycosidic enzymes such as heparin
o Allows sperm to penetrate outer layer of the egg
o The changes are facilitated by removal of glycoproteins resulting in increased membrane permeability to Ca2+
o Influx of Ca2+ leads to inc. cAMP and thus increased sperm motility
Only capacitated sperm can pass through the corona cells and undergo the acrosome reaction

Question 5

Discuss the potential for a ‘sperm factor’ in egg activation

Answer 5

• PLCzeta binds to receptors on intracellular vesicles
• PLCzeta facilitates hydrolysis of PIP2 into IP3 and DAG
• IP3 stimulates local release of Calcium ions from ER
• Oscillations of calcium release are thought to be less toxic to the cell and allow cell cycle to progress
• Cell cycle resumption by MAPK and MPF activity triggered by Ca2+ release

Question 6

Discuss the evidence for the role of PLCzeta in stimulating calcium oscillations

Answer 6

• CRISPR/CAS9 used to generate PLCzeta knockout mice

- PLCzeta KO sperm do not trigger Ca oscillations

Question 7

What factors induce the acrosome reaction?

Answer 7

Progesterone secreted by the cumulus oophorous

Calcium ion influx

Question 8

Discuss the experimental evidence for foetal programming argument (examples of fetal undernutrition)

Answer 8

• Hertfordshire cohort
• Dutch hunger famine
• 330,768 Swedish Men Born 1973-1981 Men born light
  for gestational age (<2SD scores) at increased risk of
  raised systolic blood pressure (>140mmHg, OR 1.14
  95% CI 1.07-1.22)
  • ALSPAC (children of the ‘90s) cohort; Low birthweight
  with rapid early growth associated with reduced insulin
  sensitivity Ong et al, Diabetologia 2004
  • Kings Medical Students Arterial stiffness index
  proportional to birthweight Broyd, et al, J Hypertens
  2005

Question 9

What associations were found in large population study on foetal programming by Reynolds et al?
Other further studies to support this argument?

Answer 9

Maternal obesity in pregnancy and premature mortality from cardiovascular events in adult offspring - Rebecca Reynolds

inc. in mortality with maternal obesity
- Jerusalem study –> maternal pre-pregnancy BMI and gestational weight gain rx of offspring obesity

Question 10

Define the word orexigenic

Answer 10

An appetite stimulant that may induce hyperphagia