Endocrinology of Pregnancy Flashcards
Where is tubular fluid reabsorbed and what controls this process?
Rete testis/Early epididymis
This is under the control of oestrogen
Where do you find oestrogen within the male reproductive tract?
Tubular fluid produced by sertoli cells
What stimulates the release of nutrients and other molecules (e.g. glycoproteins) into the epididymal fluid?
Androgens
What are the roles of these secreted nutrients and molecules?
Provide energy for the impending journey Coat the surface of the spermatozoon (to protect them from the hostile environment)
Within which part of the male reproductive tract is fluid reabsorbed and secretory products put in?
Epididymis
Why is the concentration of sperm in the vas deferens higher than further down the reproductive tract?
Further down the reproductive tract, other fluids and secretory products are added thus diluting the sperm.
Where is a vasectomy performed?
Lower end of the vas deferens
Which structures contribute to the seminal fluid?
Seminal vesicle (2/3)
Prostate (1/3)
Epididymis/testes (small contribution)
Why is there fibrinogen and fibrinolytic enzymes in the seminal fluid?
After ejaculation, the semen initially clots and then must be broken down
Describe the capability of the spermatozoa in the seminiferous tubule.
Quiescent and incapable of fertilising an ovum
Describe the capabilities of the spermatozoa in the vas deferens.
Capable of limited movement Limited capability to fertilise an ovum
When do sperm achieve full activity and capability achieved and what is the name given to this process?
Capacitation
This occurs within the female reproductive tract (Usually ionic and proteolytic environment of fallopian tube)
What 3 changes take place in capacitation?
Loss of glycoprotein coat
Change in surface membrane characteristics (leading to acrosome reaction when in close proximity to the ovum)
Whiplash movements of the tail
What are all these changes dependent on?
Oestrogen
Calcium
Describe the acrosome reaction.
Spermatozoon binds to ZP3 glycoprotein on zona pellucida
Once bound to ZP3, progesterone stimulates Ca 2+ influx into the spermatozoon
Results in calcium-dependent acrosome reaction
This enables exposed spermatozoon recognition site to bind to ZP2
Once bound to ZP2, the acrosome releases enzymes allowing penetration of the zona pellucida
Head of the spermatozoon can enter the ovum
Where does fertilisation normally occur?
Fallopian tube (Otherwise ectopic pregnancy)
What does fertilisation result in the expulsion of?
Second polar body
The zonal reaction immediately follows fertilisation. Describe the zonal reaction.
Cortical granules release molecules that degrade the zona pellucida (including ZP3 and ZP2) This prevents further binding of other sperm
This is also CALCIUM dependent
Describe how the conceptus receives nutrients before implantation.
Uterine secretions
How long is this free-living phase of the conceptus?
9-10 days
In what stage of the menstrual cycle is all of this occurring?
Luteal phase – oestrogen and progesterone are high
How does the egg develop into a blastocyst?
Fertilized egg -> 2 cell conceptus -> 4 cell conceptus
-> 8 cell conceptus -> compaction into 12-6 cell Morula -> blastocyst
What are the parts of the blastocyst?
Blastocoelic cavity,
Inner cell mass (embryo)
Chorion made of trophoblast cells
What is required for implantation?
Progesterone dominance
Presence of Oestrogen
What are the phases of implantation?
Attachment - outer trophoblast cells contact uterine surface epithelium
Decidulisation phase - underlying uterine stromal tissue changes (within few hours)
What is a decidua?
Thick layer of modified mucous membrane, which lines the uterus during pregnancy and is shed with afterbirth
State 2 molecules that are of particular importance in implantation. Mention which cells produce these molecules.
Leukaemia inhibitory factor (LIF) Produced by endometrial secretory glands. Stimulates adhesion (attachment) of blastocyst to endometrial cells
IL-11 Also released from endometrial cells and released into uterine fluid
Other molecules minor involvement e.g HB-EGF
What changes occur in decidulisation?
Increased vascular permeability in the invasion region, associated with oedema of tissues
Localised changes in intracellular composition and progressive sprouting and growth of capillaries
Glandular epithelium secretion
Glycogen accumulation in stroma
Which chemical factors are involved in decidualisation?
Mainly IL-11
Histamines
Certain prostaglandins
TGF-beta = promotes angiogenesis
What is the role of hCG and when does it peak?
Peaks at 8 weeks and is particularly important in the first 6 weeks It mimics LH by binding to LH receptors on the corpus luteum and stimulating the production of oestrogen and progesterone NOTE: hCG is produced by trophoblast cells
What hormonal change occur after 40 days?
The role of hormone production is handed over from the corpus luteum to the placenta
How do maternal hormones change in pregnancy?
Increase:
ACTH, adrenal steroids, prolaction, IGF 1
(GH variant present in placenta triggers this)
Iodothyronines (hCG triggers as alpha subunit resembles TSH)
PTH related peptides
Kisspeptin
Oestrogen and Progesterone (Progesterone remains dominant)
Decrease:
Gonadotrophins
Pituitary GH
TSH
What is human placental lactogen? Describe its roles.
It is a growth hormone that has prolactin like effects It is important for the growth and development of the foetus
After what point would oophorectomy have no effect on pregnancy and why?
After 40 days By this point the placenta would have taken over the role of hormone production so the ovaries are no longer needed
Which steroid precursor tends to be provided by the mother for the foetus?
Pregnenolone
Which androgen is formed by the maternal and foetal adrenals?
Dehydroepiandrosterone Sulphate (DHEAS)
This is used as a precursor for oestrogen production.
Oestradiol and Oestrone aren’t a good measure of foetal health. Explain why.
They are dependent on precursor production from the both the foetal AND maternal adrenals. Therefore, it is not a good measure of foetal health.
What is the main oestrogen of pregnancy and how is it produced?
OESTRIOL
DHEAS from the foetal adrenals is conjugated in the foetal liver to form 16-alpha-hydroxy DHEAS 16-alpha-hydroxy
DHEAS is then de-conjugated in the placenta and used to produce oestriol
What can be measured to gauge the health of the foetus?
Oestriol: oestradiol + oestrone levels
Oestriol: total oestrogens
What biochemical change is required for contraction of the uterus during parturition?
Increase in intracellular calcium concentration
Describe how oestrogen increases the chance of contraction.
Oestrogen binds to oestrogen receptors and triggers the synthesis of prostaglandins within the endometrial cells. Prostaglandins stimulate the release of calcium from intracellular stores. So oestrogen tends to increase the chance of contraction
Describe how oxytocin increases the chance of contraction.
Oxytocin binds to its receptor on the endometrial cell and opens calcium channels, allowing calcium ions to move in from outside
Describe the effect of progesterone on this contraction process.
Progesterone keeps the effects of oestrogen under control Progesterone inhibits oestrogen receptors Progesterone inhibits the production of prostaglandins
What change occurs when the foetus reaches a particular size, which is crucial for contraction to take place?
There is a switch in steroid synthesis from progesterone synthesis to oestrogen synthesis This leads to oestrogen dominance –> prostaglandin production –> calcium release from intracellular stores –> promotion of muscle contraction
What 2 hormones are involved in milk production and milk ejection?
Prolactin – milk production
Oxytocin – milk ejection
These both have a similar neuroendocrine reflex arc stimulated by suckling
