4.10 - Endocrinology of Pregnancy

Question 1

What path do the spermatozoa take after the testis?

Answer 1

• into efferent ducts where tubular fluid is reabsorbed resulting in concentrated fluid (induced by oestrogen)
• then enter epididymis where nutrients (e.g. fructose for energy for sperm journey) and glycoproteins (protective coating for sperm) are secreted into epidydimal fluid (induced by androgens)
• travels 100,000x its length from testis to fallopian tube
• equivalent to 150km for a 1.5m human

Question 2

What makes up semen?

Answer 2

• spermatozoa - 15-120 million/ml
• seminal fluid - 2-5 ml
• leukocytes
• potentially viruses e.g. hepatitis B, HIV

Question 3

How many spermatozoa in ejaculate enter cervix, then ovum?

Answer 3

• 1/100 of spermatozoa in ejaculate enter the cervix
• 1/10000 from cervix to ovum
• therefore 1/1,000,000 reach ovum overall

Question 4

Where does seminal fluid come from?

Answer 4

• small contribution from epididymis/testis
• mainly from accessory sex glands - seminal vesicles, prostate, bulbourethral glands

Question 5

What is capacitation of sperm?

Answer 5

• achieving fertilising capability in the ionic and proteolytic environment of the fallopian tube

Main changes are:

1. loss of glycoprotein ‘coat’
2. change in surface membrane characteristics
3. develop whiplash movements of tail

• oestrogen and calcium dependent

Question 6

What happens when the sperm reaches the ovum?

Answer 6

• fertilisation occurs
• sperm binds to sperm receptor - ZP3 glycoprotein
• Ca2+ influx into sperm stimulated by progesterone
• release of hyaluronidase and proteolytic enzymes from acrosome
• spermatozoon penetrates zona pellucida (glycoprotein layer surrounding plasma membrane of oocyte)

Question 7

What happens during fertilisation?

Answer 7

• occurs within fallopian tube - in ampulla
• triggers cortical reaction –> cortical granules release molecules which degrade zona pellucida (e.g. ZP2 and ZP3)
• this prevents further sperm from binding as there are no receptors left
• cell goes from haploid to diploid

Question 8

What are the stages for the development of conceptus after fertilisation?

Answer 8

• cell continues to divide as it moves down fallopian tube to uterus (3-4 days)
• receives nutrients from uterine secretions
• this free-living phase lasts 9-10 days
• inner cell mass will form the embryo

Question 9

What is the attachment phase (1) of implantation?

Answer 9

• outer trophoblast cells contact uterine surface epithelium
• leukaemia inhibitory factor (LIF) from endometrial cells stimulate adhesion of blastocyst to endometrial cells
• interleukin-11 (IL11) also from endometrial cells is released into uterine fluid and may be involved
• many other molecules like HB-EGF are involved too

Question 10

What is the decidualisation phase (2) of implantation?

Answer 10

• endometrial changes due to progesterone within a few hours of attachment:
• glandular epithelial secretion
• glycogen accumulation in stromal cell cytoplasm (connective tissue under epithelium)
• growth of capillaries (increased blood supply to support pregnancy)
• increased vascular permeability (–> oedema) to increase nutrients and O2 going to potential implanted embryo
• IL11, histamine, certain prostaglandins and TGFbeta (promotes angiogenesis) are involved

Question 11

When do these stages of implantation occur and what do they require?

Answer 11

• attachment and decidualisation occur in the luteal phase
• require progesterone domination in the presence of oestrogen

Question 12

How do different hormone levels change during pregnancy?

Answer 12

• hCG - peaks just before 10 weeks then decreases
• human placental lactogen - made by placenta and modulates maternal metabolism to provide nutrients for foetus e.g. causes insulin resistance in mother so more glucose available for foetus - increases
• oestrogens - increases
• progesterone - peaks around 40 weeks

Question 13

Why is hCG tested for in a pregnancy test?

Answer 13

Since it is only made by placenta so would show there is a developing foetus if present in urine

Question 14

What hormones are made in the first 40 days?

Answer 14

• progesterone and oestrogen
• produced in corpus luteum (maternal ovary)
• stimulated by hCG (produced by trophoblasts) which acts on LH receptors
• essential for developing fetoplacental unit
• inhibits maternal LH and FSH (-ve feedback)

Question 15

What hormones are made from day 40 onwards?

Answer 15

• oestrogen and progesterone
• placenta takes over
• main substitute for oestrogen is DHEAS which can be made by both mother and foetus

Question 16

What maternal hormones increase in pregnancy?

Answer 16

• ACTH - meaning raised urinary free cortisol (UFC)
• adrenal steroids
• prolactin - suppresses HPG axis
• IGF-1 - stimulated by placental GH-variant
• iodothyronines - due to increased requirement, driven by hCG which has same alpha subunit as TSH = lower TSH
• PTH related peptides - produced mainly in breast tissue and can increase Ca2+ for foetal skeleton

Question 17

What maternal hormones decrease in pregnancy?

Answer 17

• gonadotrophins (FSH and LH)
• pituitary GH - decreases as placental GH increases
• TSH

Question 18

What effects does oxytocin have on pregnant women?

Answer 18

• uterine contraction - with increased numbers of oxytocin receptors in late pregnancy
• cervical dilation
• milk ejection
• also cortisol and oestrogen contribute

Question 19

What can hyperprolactinaemia cause related to milk production?

Answer 19

Excess milk production –> galactorrhoea - leaking of milk even outside pregnancy

Question 20

Why does a prolactinoma cause decreased LH, FSH and oestrogen?

Answer 20

• prolactinoma - tumour in pituitary that produces excess prolactin
• excess prolactin has an inhibitory effect on GnRH = less GnRH released = less gonadotrophin released (LH&FSH) = low oestrogen and absent periods (amenorrhoea)