The Endocrinology of Pregnancy

Question 1

What do Sertoli cells make?

Answer 1

Spermatozoa and oestrogen

Question 2

What do Leydig cells produce?

Answer 2

Testosterone

Question 3

Where are sertoli cells found?

Answer 3

In the seminiferous tubules within the testes

Question 4

Give 3 symptoms of aromatase deficiency (thus oestrogen deficiency) in males and why they occur

Answer 4

1. Infertile - oestrogen is important for tubular fluid reabsorption within the rete testis and early epididymis
2. Osteoporosis - oestrogen plays a role in bone turnover
3. Tall - oestrogen is needed to close the growth plates

Question 5

What happens in aromatase deficiency that causes symptoms in females and give 3 specific symptoms that females experience

Answer 5

• Aromatase deficiency causes less conversion of testosterone into oestrogen in the steroid biosynthetic pathway so there is a defiency in oestrogen and a build-up of testosterone which both cause symptoms. Virilisation

1. Hirsutism
2. Deepening voice
3. Amenorrhoea

Question 6

Where and how is tubular fluid reabsorbed?

Answer 6

• In the rete testis and the early epididymis
• Induced by oestrogen

Question 7

Where would you find oestrogen in the male reproductive system?

Answer 7

Mainly in tubular fluid produced by Sertoli cells

Question 8

What secretions occur into the tubular fluid as it becomes the epididymal fluid (as it enters the epididymis), and what is the function of these secretions?

Answer 8

• Fructose - provide energy for the journey
• Glycoproteins - coat the surface of the spermatozoa (to protect them from the hostile environment)

Question 9

What does semen consist of?

Answer 9

• Spermatozoa
• Seminal fluid
• Leucocytes
• Viruses possibly - Hep B, HIV etc

Question 10

Why does the concentration of spermatozoa decrease further down the male reproductive tract from the vas deferens to the urethra?

Answer 10

Because you add fluid as you go

Question 11

Where are the 3 main sites of seminal fluid production, and where are 2 other minor sites of seminal fluid production?

Answer 11

Main

1. Prostate
2. Bulbourethral gland
3. Seminal vesicles

Minor

1. Testes
2. Epididymis

Question 12

How is seminal fluid concentrated, and what hormone induces this?

Answer 12

Concentrated by tubular fluid reabsorption as induced by oestrogen

Question 13

1) What is the principle of the need for capacitation of sperm?
2) In what environment and where does sperm capacitation take place?
3) What 2 things is sperm capacitation dependent upon?
4) Give 3 things that happen to sperm in sperm capacitation

Answer 13

1)

• Sperm is quiescent within the seminferous tubules and has limited movement and capability within the vas deferens. Sperm capacitation is the activation of the full fertilising capability of the sperm within the female reproductive tract

2)

• Within the ionic and proteolytic environment of the female reproductive tract

3)

• Oestrogen-dependent
• Ca²⁺ dependent

4)

1. Lose their glycoprotein coat
2. Change in the surface membrane characteristics
3. Develop whiplash movements of their tails

Question 14

Describe the acrosome reaction for fertilisation

Answer 14

1. Spermatozoon acrosome binds ZP3 glycoprotein receptor on oocyte
2. Ovum secretes progesterone which stimulates Ca²⁺ influx into spermatozoon
3. Simultaneous secretion of both proteolytic enzymes and hyaluronidase (polsaccharide enzyme) to break down the zona pellucida glycoprotein layer surrounding the oocyte

Question 15

How does one spermatozoon prevent another binding to the same oocyte during fertilisation?

Answer 15

Once one spermatozoon binds an oocyte, it triggers a cortical reaction in the zona pellucida that blocks more sperm binding - cortical granules release molecules that degrade the ZP2/3 receptors on the zona pellucida of the oocyte to prevent another spermatozoon binding

Question 16

How is a second polar body formed in the female oocyte maturation pathway?

Answer 16

There is an even mieotic division of chromosomes at one point, but uneven cytoplasm distribution - generating one viable oocyte with lots of cytoplasm and a second polar body with insufficient cytoplasm which gets degraded

Question 17

1) What is the free-living phase of fertilised eggs, and how does it last?
2) What actual phase during menstruation does this free-living phase occur and so what hormones are high in concentration at this time?

Answer 17

1)

• The phase wherein the fertilised egg migrates from the fallopian tube down to the uterus, all the while developing and receiving nutrients from uterine secretions, prior to endometrial attachment
• Lasts for 9-10 days

2)

• During the luteal phase
• Oestrogen and progesterone

Question 18

1) Outline the development process of the conceptus / zygote during the free-living phase including…
2) …What promotes the transfer to the uterus?

Answer 18

1)

1. Fertilised egg divides to form 2-cell compactus
2. 2-cell divides again and again and possibly again until you have an 8 or 16-cell compactus
3. This undergoes compaction to form a morula
4. This eventually develops into a blastocyst with an inner cell mass which becomes the embryo, a blastocystic cavity and outer trophoblast cells which becomes the chorion and thence the placenta

2)

• The high progesterone:oestrogen ratio that occurs in the luteal phase promotes transfer of the developing zygote to the uterus

Question 19

What are the 2 phases of endometrial implantation of the zygote?

Answer 19

1. Attachment
2. Decidualisation

Question 20

1) What essentially happens in the attachment phase of implantation?
2) What 2 substances are important in the attachment phase, where are they secreted from / into (where applicable) and what stimulates their release?

Answer 20

1)

• Outer trophoblast cells of the blastocyst attach to the uterine surface epithelium - endometrium

2)

1. Leukemia Inhibitory Factor (LIF) - secreted from endometrial cells, stimulated by TGF, TNF, IL-1, Hb-EGF, Leptin, Progesterone
2. IL-11 - released from endometrial cells, released into uterine fluid, stimulated by TGF, TNF, IL-1, Relaxin, PGE₂

Question 21

1) What happens in the decidualisation reactions of endometrial implantation?
2) What factors are involved in these?

Answer 21

1)

• Glandular epithelial secretion of nutrients
• Glycogen accumulation in stromal cell cytoplasm (under epithelium)
• Capillary growth (to improve blood supply)
• Increased vascular permeability (→oedema)

2)

• IL-11
• Histamine
• Certain prostaglandins
• TGF-ß (promotes angiogenesis)

Question 22

What are the main 4 hormone changes that are noticeable during pregnancy at first?

Answer 22

• At first there is a rise in hCG
• Rise in oestrogen
• Rise in progesterone
• Rise in human placental lactogen

Question 23

What happens to progesterone and oestrogen production, and what is the role of hCG…

1) In the first 40 days of pregnancy?
2) After the first 40 days of pregnancy?

Answer 23

1)

• Corpus luteum secretes oestrogen and progesterone
• This is stimulated by hCG acting on LH receptors
• hCG also prevents the increased oestrogen from having loads of negative inhibition on the LH / FSH

2)

• Placenta takes over oestrogen and progesterone production
• Not driven by hCG / LH / FSH

Question 24

Label this diagram of the foeto-placental hormone axis

Answer 24

Question 25

What precursors does the mother provide in the foeto-placental hormone axis?

Answer 25

1. Cholesterol
2. Pregnenolone
3. Progesterone

Question 26

How is oestradiol produced in the foeto-placental hormone axis?

Answer 26

1. Cholesterol → pregnenolone → progesterone → DHEAS from foetal andrenals and foetal liver OR DHEAS directly from mother
2. DHEAS converted into oestradiol in the placenta by de-conjugation

(same as oestrone)

Question 27

How is oestrone produced in the foeto-placental hormone axis?

Answer 27

1. Cholesterol → pregnenolone → progesterone → DHEAS from foetal andrenals or liver OR DHEAS directly from mother
2. DHEAS converted into oestrone in the placenta by de-conjugation

(same as with oestradiol)

Question 28

How is oestriol produced in the foeto-placental hormone axis?

Answer 28

Cholesterol from mother → pregnenolone (or just directly pregnenolone from mother) → progesterone → taken up by foetus → foetal adrenals form DHEAS → liver conjugates DHEAS to form 16α-hydroxy DHEAS → deconjugated in the placenta to form oestriol

Question 29

What are the 3 forms of eostrogens formed in pregnancy, and which is the only one formed exclusively by the foetus?

Answer 29

1. Oestradiol
2. Oestrone
3. OESTRIOL - main, purely foetal

Question 30

In terms of the oestrogens formed in pregnancy, how could you use them as metrics for when to be worried about the foetus and why?

Answer 30

• Look at ratio of oestriol:oestradiol +oestrone or oestriol:total oestrogens
• If this changes (increases?) then be worried as oestriol is the only one made exculsively by the foetus

Question 31

List 6 maternal hormones that increase during pregnancy

Answer 31

1. ACTH
2. Adrenal steroids
3. Prolactin
4. IGF-1 (stimulated by placental GH-variant)
5. Iodothyronines - increased demands for thyroid hormones in pregnancy
6. PTH related peptides

Question 32

List 3 maternal hormones that decrease during pregnancy

Answer 32

1. Gonadotrophins
2. Pituitary GH
3. TSH

Question 33

2 ways to assess whether a woman is ovulating?

Answer 33

1. Day-21 progesterone test - this can only come from the corpeus luteum which is only present after ovulation
2. U/s test

Question 34

Describe the hormonal control of parturition including 2 hormones that promote parturition and one hormone that inhibits it

Answer 34

• Parturition involves actin and myosin filament contraction requiring calcium - you need to increase [calcium] and intake
• Oestrogen stimulates production of prostaglandins which release intracellular calcium stores to promote actin-myosin contraction (and increases amounts of oestrogen receptors)
• Progesterone inhibits prostaglandin release (and lowers number of oestrogen receptors)
• Oxytocin released on parturition and binds receptors to open calcium channels to promote actin-myosin contractility also
• Also needs increased oestrogen:progesterone from the foetus (occurs when it grows larger) to stimulate prostaglandin and oxytocin release to promote contractility

Question 35

What does it mean to be hypogonadotrophic in regards to hormones?

Answer 35

• Low LH /FSH

Question 36

Outline the lactation (milk letdown) neuro-endocrine reflex arc in full

Answer 36

1. Suckling stimulus
2. Neural afferent pathways to the hypothalamus
3. Pituitary then secretes prolactin from the adenohypophysis and oxytocin from the neurohypophysis
4. Prolactin promotes milk synthesis and oxytocin promotes milk ejection

Question 37

What does it mean to have hypogonadism in regards to hormones?

Answer 37

• Low testosterone / oestrogen

Question 38

Describe briefly when and if hCG, oestrogen, progesterone and human placental lactogen rise in pregnancy

Answer 38

• hCG rises at first then falls later on in term when there is placental independence (no longer dependent on hCG stimulation of corpus luteum to secrete oestrogen and progesterone)
• Human placental lactogen high throughout
• High progesterone and oestrogen at start and high progesterone : oestrogen near start but as you go on there is a fall in both but a sharper fall in progesterone until you get a higher oestrogen : progesterone ratio