Endocrinology of Pregnancy Flashcards
Fertilization of an ovum:
- normally occurs in the uterus
- requires a fully capacitated spermatozoon
- depends on the spermatozoon penetrating the zona pellucida around the ovum
- is accompanied by the expulsion of the second polar body
- necessitates a progesterone-dominated environment
False
True
True
True
True
Implantation:
- occurs approximately 30 days after fertilization
- is initiated by the free-floating blastocyst
- is non-invasive in humans
- requires an initial attachment phase
- is successful only in an oestrogen-free environment
False True False True False
Decidualization:
- involves the breakdown of the uterine stroma underlying the attaching blastocyst
- provides nutrients for the implanting blastocyst
- occurs within a few hours of attachment
- necessitates the presence of both progestogen and oestrogen
- is initiated by molecules including histamine and prostaglandins
True True True True True
During pregnancy:
- Oestradiol is the principal oestrogen produced by the fetoplacental unit
- Placental hCG (human chorionic gonadotrophin) acts on ovarian LH receptors
- Maternal pituitary gonadotrophin production increases throughout
- Progesterone is the dominant steroidal influence until parturition
- HPL (human placental lactogen) stimulates breast development
False True False True True
At Parturition:
- the fetal production of corticotrophin (ACTH) switches steroid production towards oestrogen domination
- oestrogen stimulates myometrial prostaglandin synthesis
- oxytocin induces myometrial contractions
- progesterone stimulates the myometrial synthesis of oxytocin receptors
- there is a maternal pituitary LH surge
True True True False False
What is the bulbourethral gland?
Two pea-shaped glands in the male, located beneath the prostate gland at the beginning of the internal portion of the penis; they add fluids to semen during the process of ejaculation
Where do spermatozoa form? What surrounds them?
Spermatozoa form in the middle of the seminiferous tubules
This is surrounded by Sertoli cells which are needed to make sperm
Where is testosterone made?
Made by Leydig cells in the interstitium
What is tubular fluir reabsorption induced by in males? What does this do?
Tubular fluid reabsorption is induced by oestrogen in men - this concentrates the sperm
What stimulates secretion of nutrients and glycoproteins into epididymal fluid and why is this needed?
Stimulated by ANDROGENS
Needed for the protective coating of sperm
What are the contents of semen?
- Spermatozoa - 15-20million/ml
- Seminal fluid 2-5ml
- Leucocytes
- Potentially viruses like HepB, HIV
What is seminal fluid?
The fluid in which sperm swim
How many sperm actually reach the ovum?
about 1/million sperm
What are the accessory sex glands?
Seminal vesicles
Prostate
Bulbourethral gland
Where is seminal fluid mostly produced?
Mostly from accessory sex glands
Small contribution from epididymis/testis
What is capacitation and where does it occur?
- Capacitation = achieving the ability to fertilise
- Occurs in the FEMALE REPRODUCTIVE TRACT
What are the 3 main events of capacitation?
- Loss of glycoprotein “coat”
- Change in surface membrane characteristics
- Development of whiplash movements of the tail
What is needed for capacitation to occur?
- Ionic and proteolytic environment of the Fallopian tube
- Oestrogen-dependent
- Ca2+-dependent
What is the acrosome?
Acrosome - small organelle which contains enzymes and binds to the zona pellucida
What is the zona pellucida?
Zona pellucida= glycoprotein layer around the ovum which has ZP3 glycoprotein receptors (sperm receptors)
What happens in the acrosome reaction?
- Sperm binds to ZP3 (=sperm receptor)
- Ca2+ influx into sperm (stimulated by progesterone)
- Release of hyaluronidase and proteolytic enzymes (from the acrosome organelle)
- —> Spermatozoon can then penetrate the zona pellucida
Where does fertilisation occur?
What is it called when it happens outside of this?
Fallopian tube
Ectopic pregnancy
What happens once the sperm infiltrate the zona pellucida?
FERTILISATION :
- A cortical reaction is triggered which releases molecules which degrade the zona pellucida
- This means that no more sperm can attach since there are no more ZP3 receptors.
- Haploid—-> diploid
Why can sperm no longer attach after the cortical reaction?
Zona pellucida is degraded so no more ZP2 or ZP3 receptors present
How long can the free-living phase of the conceptus last?
9-10 days
What happens to the conceptus after fertilisation?
- 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
Where does the conceptus receive its nutrients during the free-living phase?
Uterine secretions
Describe the formation of a blastocyst.
Fertilised egg divides into 2 cell conceptus –> 4 cell conceptus –> 8 cell conceptus –>morula (by COMPACTION) –> blastocyst
What is the early form of the embryo in the blastocyst?
Inner cell mass
What do the trophoblast cells of the blastocyst go on to become?
Chorion of the placenta
In what step does “compaction” take place?
8 cell conceptus –> morula
What are the two phases of implantation?
- Attachment phase - OUTER TROPHOBLAST cells contact the uterine surface epithelium
- Decidualisation phase - changes in underlying uterine stromal tissue (within a few hours) (this is when the blastocyst implants indefinitely)
What is required for implantation to occur?
Progesterone domination in the presence of oestrogen
Name two key factors which are required for attachement to 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
- Many other molecules involved in process (e.g. HB-EGF)
Where is LIF released from? Where is IL11 released?
Leukaemia inhibitory factor (LIF) from endometrial secretory glands (& blastocyst?)
IL11 also from endometrial cells into uterine fluid
What is decidualisation?
Endometrial changes due to progesterone. One of the two phases of implantation.
Give 4 things which happen during decidualisation.
– Glandular epithelial secretion
– Glycogen accumulation in stromal cell cytoplasm
– Growth of capillaries
– Increased vascular permeability (→oedema)
What factors are involved in decidualisation?
Interleukin-11 (IL11), histamine, certain prostaglandins & TGFb
(TGFb promotes angiogenesis)
Draw the hormonal changes which occur during pregnancy.
What is human placental lactogen needed for in pregnancy?
Calcium balance
Describe the hormones involved in the first 40 days of pregnancy and where they are produced.
Progesterone and oestrogen:
- Produced in corpus luteum (in maternal ovary) stimulated by hCG (produced by trophoblasts) and acts on LH receptors
- Essential for developing fetoplacental unit
- Inhibits maternal LH & FSH (-ve feedback)
Describe the change in where hormones are produced after day 40 of pregnancy.
Placenta takes over from the corpus luteum
What stimulates the production of oestrogen and progesterone in the first 40 days of pregnancy and how?
hCG action on the LH receptor
Where does progesterone and oestrogen production take place in the first 40 days of pregnancy? What is it needed for?
Corpus luteum (in maternal ovary) - this is the follicle where the egg came from
Needed for:
Developing fetoplacenta unit
Inhibits LH & FSH (-ve feedback)
How does the placenta make oestrogen after day 40?
DHEAS is produced in the mother and in the adrenals of the foetus.
It then goes to the placenta where it is converted to OESTRADIOL/OESTRONE
List the maternal hormones which increase during pregnancy.
- ACTH –> high cortisol
- Adrenal steroids
- Prolactin
- IGF1 (stimulated by placental GH-variant)
- Iodothyronines (about 30% more needed)
- PTH related peptides
List the maternal hormones whcih decrease during pregnancy.
- Gonadotrophins
- Pituitary GH
- TSH
Mostly due to high hCG levels
Why do iodothyronines increase in pregnancy?
T4 and T3 increases to help support the body
- this is driven because hCG shares an alpha subunit with TSH so high hCG levels will also stimulate the increased need for iodothyronines in pregnancy - you need about 30% more
Where does oxytocin come from?
Posterior pituitary
Neurohypophysis
Parturition = labour
Describe how oxytocin is involved in parturition.
- Oxytocin binds to the oxytocin receptors (which increase in number during pregnancy) on the endometrial muscles.
- There is also some input from oestrogen.
- This increases contraction of the uterus during pregnancy.
Summarise the processes involved in lactation.
Suckling (mechanical stimulation) activates neural pathways to the hypothalamus
Hypothalamus stimulates the pituitary to produce prolactin and oxytocin which are required for mik production and milk ejection respectively.
What are the two hormones required for lactation to occur? Where are they produced?
Produced by pituitary
Adenohypophysis (anterior pituitary) –> prolactin
Neurohypophysis –> oxytocin
What is the function of prolactin and oxytocin in lactation?
Oxytocin - ejection of milk
Prolactin - production of milk
Why do athletes get amenorrhoea/loss of libido?
High prolactin levels in athletes –> loss of libido/amenorrhoea
High prolactin is produced by the stimulation of their nipples by their shirt
Prolactin then binds to kisspeptin neurons which are inhibited at the very top of the reproductive axis so nothing works below.
