Endo 11: Endocrinology of pregnancy

Question 1

Role of oestrogen in male reproductive system?

Answer 1

oestrogen regulates the reabsorption of luminal fluid in the head of the epididymis

Question 2

How do men get their oestrogen

Answer 2

Aromatisation of testosterone produced by Leydig cells

Question 3

Consequences of aromatase deficiency in men (very rare)

Answer 3

Infertile and very tall as oesterogen needed to turn of growth plates

Question 4

Functin of androgen in sperm production

Answer 4

Nutrients & glycoprotein
secretion into epididymal fluid
(induced by androgens)

Question 5

How much sperm in ejaculate

Answer 5

15-120 million/ml

Question 6

Contents of ejaculation

Answer 6

15-120 million/ml
Seminal fluid 2-5m
Leucocytes
(potentially viruses e.g. hepatitis B, HIV)

Question 7

How many sperm enter the cervix and get totthe ovum in each

Answer 7

1/100 of spermatozoa in ejaculate enter the cervix

• 1/10,000 cervix to ovum

Question 8

which organs secrete the seminal fluid

Answer 8

Small contribution from:
– Epididymis/testis

• Mainly from accessory sex glands:
– Seminal vesicles
– Prostate
– Bulbourethral glands

Question 9

What is the funtion of capacisation of sperm

Answer 9

Achieve fertilising capability in the female repro tract

Question 10

What are the 3 stages of capacitsaiton

Answer 10

1. Loss of glycoprotein ‘coat’
2. Change in surface membrane characteristics
3. Develop whiplash movements of tail

Question 11

Where does capacitation of sperm occur, which enzyme does it dependd on, and what ion is it dependent on

Answer 11

• Takes place in ionic & proteolytic environment of the Fallopian tube
• Oestrogen-dependent
• Ca2+-dependent

Question 12

To which receptor does sperm bind

Answer 12

Sperm binds to ZP3 (= sperm receptor) (on the Zona Pellucida, thus ZP3!)

Question 13

What follows sperm binding to ZP3

Answer 13

Ca2+ influx into sperm (stimulated by progesterone)
• Release of hyaluronidase & proteolytic enzymes (from Acrosome)

Spermatozoon penetrates zona pellucida

Question 14

Where does fertilisation occur

Answer 14

within the Fallopian tube

Question 15

What reaction is trigggered following fertilisation and what is the consequence

Answer 15

Triggers cortical reaction

Cortical granules release molecules which degrade Zona
Pellucida (e.g. ZP2 & 3)
– Therefore prevents further sperm binding as no receptors

• Haploid Diploid

Question 16

How does conceptus develp

Answer 16

Continues to divide as it moves down Fallopian tube
to uterus (3-4 days)
• Receives nutrients from uterine secretions
• This free-living phase can last for ~ 9-10 days

Question 17

What does egg divide into

Answer 17

Fertilised egg, 2, 4 and 8 cell conceptus, COMPACTION, morula and blastocyst

Question 18

2 stages of implantation and the hormone required

Answer 18

Attachment phase: outer trophoblast cells contact uterine
surface epithelium
THEN
• Decidualisation phase : changes in underlying uterine
stromal tissue (within a few hours)

Requires progesterone domination in the presence of
oestrogen

Question 19

How does attachment occur

Answer 19

Leukaemia inhibitory factor (LIF) from endometrial
secretory glands (& blastocyst?) stimulates 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 involved in process
(e.g. HB-EGF)

Question 20

What is decidualisation

Answer 20

Endometrial changes due to progesterone
– Glandular epithelial secretion
– Glycogen accumulation in stromal cell cytoplasm
– Growth of capillaries
– Increased vascular permeability (→oedema)

Question 21

What factors are involved in decidualisatin

Answer 21

Interleukin-11 (IL11), histamine, certain prostaglandins & TGFb
(TGFb promotes angiogenesis)

Question 22

Hormone changes in pregnancy

Answer 22

hCG increases quickly at first then falls just before 10 weeks…..

progesterone increases to 35 weeks then falls

Human placental lactogen, oestrogen also important and increase

Question 23

Where is progesterone produced in the first 40 days

Answer 23

Produced in corpus luteum (in maternal ovary)

Essential for developing fetoplacental unit (remember decidualisation and then implantation requires PROGESTERONE DOMINANCE)

• Inhibits maternal LH & FSH (-ve feedback)

Question 24

Where does hCG act and where is it produced and for what reason

Answer 24

(produced by trophoblasts which are cells which turns into the placenta ) and acts on LH receptorson the ovary, to cause development of the corpus luteum and thus cause progesterone and oestrogen release in the first 40 days of pregnancy from the corpus luteum

Question 25

What happens with progesterone and oestrogen production after day 40

Answer 25

Placenta starts to take over

Question 26

How does placenta produce oestrogen

Answer 26

Placenta using DHEAS producted by mother or foetus (from mothers' pregnenolone) to make oestradio or oestrone or placenta using 16-a hydroxy DHEAS from baby liver (still using mother pregnenolone) to produce oestriol (BIG)

Question 27

What physiological changes in materna hormones

Answer 27

``` INCREASE • ACTH • Adrenal steroids • Prolactin • IGF1 (stimulated by placental GH-variant human lactose hormone) • Iodothyronines • PTH related peptides ``` DECREASE: • Gonadotrophins • Pituitary GH • TSH

Question 28

Outline control of parturition

Answer 28

Oxytocin receptor number on endometrial smooth muscle increases and this induces contraction in smooth muscle also input from oestrogen and cortisol

Question 29

Outline control of lactation

Answer 29

Anterior pit. releases prolactin leading to milk synthesis and oxytocin released which casues milk ejection. Release of both is caused by suckling (neural stimulus to the hypothalamus to cause pit. release)

Question 30

Why is having a prolactinoma problematic in pregnnacy

Answer 30

Because usually the size of the prolactinoma can be estimated from the plasma levels of prolactin During pregnancy, prolactin is elevated, so this is not reliable Instead, one performs visual field testing every trimester (possibly MRI too if necessary)

Question 31

T/F t3/t4 increases during pregnancy in response to increased TSH By how much do iodothyronines increase during pregnancy

Answer 31

F. t3/t4 does increase, but TSH decreases during pregnancy t3/t4 needs to increase by ~30% in pregnancy

Question 32

Why does t3/t4 increase in pregnancy

Answer 32

Even though TSH is reduced, these iodothyronines increase because hCG shares a subunit wit TSH, so will stimulate t3/t4 production and release from the thyroid gland

Question 33

Why does TSH reduce dring pregnancy

Answer 33

Because hCG is also stimuating the thryoid gland so not do much TSH needed

Question 34

Why does pituitary GH reduce in pregnancy

Answer 34

Because you have placental GH-variant instead (human placental growth hormone) and this can lead to the IGF1 release (somatomedin) which causes cell growth and lack of apoptosis (most potent trigger of AKT pathway)