Endo 11: Endocrinology of pregnancy Flashcards
Role of oestrogen in male reproductive system?
oestrogen regulates the reabsorption of luminal fluid in the head of the epididymis
How do men get their oestrogen
Aromatisation of testosterone produced by Leydig cells
Consequences of aromatase deficiency in men (very rare)
Infertile and very tall as oesterogen needed to turn of growth plates
Functin of androgen in sperm production
Nutrients & glycoprotein
secretion into epididymal fluid
(induced by androgens)
How much sperm in ejaculate
15-120 million/ml
Contents of ejaculation
15-120 million/ml
Seminal fluid 2-5m
Leucocytes
(potentially viruses e.g. hepatitis B, HIV)
How many sperm enter the cervix and get totthe ovum in each
1/100 of spermatozoa in ejaculate enter the cervix
• 1/10,000 cervix to ovum
which organs secrete the seminal fluid
Small contribution from:
– Epididymis/testis
• Mainly from accessory sex glands:
– Seminal vesicles
– Prostate
– Bulbourethral glands
What is the funtion of capacisation of sperm
Achieve fertilising capability in the female repro tract
What are the 3 stages of capacitsaiton
- Loss of glycoprotein ‘coat’
- Change in surface membrane characteristics
- Develop whiplash movements of tail
Where does capacitation of sperm occur, which enzyme does it dependd on, and what ion is it dependent on
- Takes place in ionic & proteolytic environment of the Fallopian tube
- Oestrogen-dependent
- Ca2+-dependent
To which receptor does sperm bind
Sperm binds to ZP3 (= sperm receptor) (on the Zona Pellucida, thus ZP3!)
What follows sperm binding to ZP3
Ca2+ influx into sperm (stimulated by progesterone)
• Release of hyaluronidase & proteolytic enzymes (from Acrosome)
Spermatozoon penetrates zona pellucida
Where does fertilisation occur
within the Fallopian tube
What reaction is trigggered following fertilisation and what is the consequence
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
How does conceptus develp
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
What does egg divide into
Fertilised egg, 2, 4 and 8 cell conceptus, COMPACTION, morula and blastocyst
2 stages of implantation and the hormone required
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
How does attachment occur
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)
What is decidualisation
Endometrial changes due to progesterone
– Glandular epithelial secretion
– Glycogen accumulation in stromal cell cytoplasm
– Growth of capillaries
– Increased vascular permeability (→oedema)
What factors are involved in decidualisatin
Interleukin-11 (IL11), histamine, certain prostaglandins & TGFb
(TGFb promotes angiogenesis)
Hormone changes in pregnancy
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
Where is progesterone produced in the first 40 days
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)
Where does hCG act and where is it produced and for what reason
(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
What happens with progesterone and oestrogen production after day 40
Placenta starts to take over
How does placenta produce oestrogen
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)
What physiological changes in materna hormones
INCREASE • ACTH • Adrenal steroids • Prolactin • IGF1 (stimulated by placental GH-variant human lactose hormone) • Iodothyronines • PTH related peptides
DECREASE:
• Gonadotrophins
• Pituitary GH
• TSH
Outline control of parturition
Oxytocin receptor number on endometrial smooth muscle increases and this induces contraction in smooth muscle also input from oestrogen and cortisol
Outline control of lactation
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)
Why is having a prolactinoma problematic in pregnnacy
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)
T/F t3/t4 increases during pregnancy in response to increased TSH
By how much do iodothyronines increase during pregnancy
F.
t3/t4 does increase, but TSH decreases during pregnancy
t3/t4 needs to increase by ~30% in pregnancy
Why does t3/t4 increase in pregnancy
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
Why does TSH reduce dring pregnancy
Because hCG is also stimuating the thryoid gland so not do much TSH needed
Why does pituitary GH reduce in pregnancy
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)
