Implantation and Pregnancy Flashcards
What is the trophoblast?
- cells of the blastocyst
- invade the endometrium and myometrium (days 5-6)
- secrete beta hCG, which maintains the CL
What is the chorion?
membranous structure
becomes the foetal aspect of the placenta
What is the amnion?
layer that becomes the amniotic sac
Which stage of fertilisation occurs in which part of the uterine tubes?
PRONUCLEAR STAGE
day 0
fimbriated infundibulum/ampulla
2-CELL ZYGOTE
24h
ampulla (thicker portion of tube)
4-CELL ZYGOTE
48h
moving more medially from ampulla to isthmus
MORULA
day 4 (96h)
moving medially towards the corpus of uterus
BLASTOCYST
Day 5 (120h)
enters uterus
secretes proteolytic enzymes to degrade the ZP
implants in posterior wall of endometrium
What is the time window for fertilisation to occur?
once released, oocyte can only be fertilised for <24h
enters uterus as blastocyst ~5d later
timing is crucial for CL maintenance and endometrial change
What changes must occur for implantation?
- differentiation of the trophoblast
- trophoblastic invasion of the decidua and myometrium
- remodelling of maternal vasculature in utero-placental circulation
- development of vasculature within trophoblast
What is the decidua?
pregnant endometrium
What occurs during implantation?
DAY 5-6
implantation window
24-36h
DAY 10 trophoblast produces hCG (maternal recognition of pregnancy) CL is maintained, P produced P causes decidualisation of the endometrium
What is the purpose of decidualisation?
mediated by P (produced by CL)
which promotes steroidogenesis in CL during first trimester
vital until placental steroidogenesis is established (<7wks)
What is beta hCG?
basis of urinary pregnancy tests (qualitative)
beta hCG levels maximal by 9-11 wks
serum hCG: quantitative
- useful for monitoring early pregnancy complications e.g. ectopic, miscarriage
What is the structure of hCG?
2 subunits (alpha and beta) joined by 2x disulphide bonds
serum/urinary hCG testing: detects beta subunit
hence called BETA hCG testing
Does the urinary beta hCG test pick up LH?
no.
contains Ab targeting the beta subunit of hCG
this is different in LH and therefore will not pick up LH
How do hCG levels change during pregnancy?
4-8 WKS
exponential rise in levels
MISCARRIAGE
falling hCG in this time (early pregnancy)
ECTOPIC PREGNANCY
rise in hCG and then fall during early pregnancy
(if fall is sufficient, surgery to remove ectopic may not be required)
What are the functions of the placenta?
- steroidogenesis: oestrogen, progesterone, hPL, cortisol
- nutrients: provision of maternal O2, CHO, fats, AAs, vitamins, minerals, Ab (IgG)
- waste products: removal of CO2, urea, NH4, minerals
- barrier to pathogens, drugs etc
How many types of oestrogen are there?
LEAST POTENT E1: (one OH group) E2: menstrual cycle E3: pregnancy MOST POTENT
What adaptations does the placenta have to aid function?
huge maternal uterine blood supply: low pressure
huge reserve in function
huge SA, in contact with maternal blood
highly adapted + efficient transfer system
What are the different types of trophoblast cells?
SYNCYTIOTROPHOBLASTs
contains no PMs, just one large multinucleate entity
spread out and mediate multiple contact points for embedding in uterine wall
CYTOTROPHOBLASTs
found within the syncytiotrophoblast
contain PMs
What is the function of the extra-embryonic mesoderm?
surrounds the embryo
will go onto form the foetal blood supply
How does the placental and foetal blood network develop?
initially have lakes of maternal blood that form (LACUNAE)
invasion of trophoblasts into the lacunae and mesoderm
trophoblasts get thinner as this happens
this allows the formation of maternal and foetal blood vessels
whilst the vessels run very close to each other, there is no direct contact between
the maternal and foetal blood, so no mixing occurs
What changes to the foetal blood supply occur between the 1st and 2nd trimester?
branching of vessels
allowing closer contact between maternal and foetal blood
(~1 membrane endothelium) distance between them)
What is the vessel composition of the umbilical cord?
normally 3 vessels:
- 2 arteries
- 1 vein
variations to this exist - “2 vessel baby”
What is the function of the amniotic cavity?
HOMEOSTASIS
temperature
fluid
ions/electrolytes
DEVELOPMENT
limbs
lungs etc
PROTECTION
physical barrier
e.g. ascending infection
What is the composition of amniotic fluid?
essentially foetal urine
minus the waste products
(which are excreted by maternal kidneys)
What info does premature membrane rupture provide about foetal development?
Premature (16-17wks)
abnormal limb and lung development often seen in premies
=> fluid is v. important for correct development
What are the main barriers that protect the foetus from infection?
- cervical mucous plug
- amniotic membrane
prevents entry of microbes from vaginal canal
PATHOLOGY: if abnormalities in membrane, can increase risk of gestational infection
What does the septum transversum go on to form?
formation during neural folding process
will go on to form the thoracic cavity and abdominal mesentery
What does the rotation and fusion of the neural folds go on to develop?
will become the CNS/brain matter
How does the amnion develop into the amniotic sac?
initially it is laid on top of the ectoderm and neural fold
folding of this entire structure, occurs downwards towards the yolk sac and umbilical stalk
this causes wrap-around structure of the amniotic sac
What are the main disorders of the placenta?
- miscarriage (15-40% of pregnancies)
- pre-eclampsia (10% of pregnancies)
- hydatiform mole (rare)
- placental insufficiency
- transfer of other substances e.g. drugs, toxins, infections
What is a hydatidiform mole?
= molar pregnancy
rare, occurs in early pregnancy
genetically abnormal or excessive growth of trophoblast
contains male DNA only, oocyte has been expelled or is anuclear
What is a common cause of miscarriage?
abnormal placental morphology and function
What is placental insufficiency?
often associated with pre-eclampsia
recognised when weeks of gestation do not correlate with growth parameters for mum
What infections may cause placental disorders?
(usually maternal transfer)
- HIV
- Chlamydia
What are disorders of the amnion?
- polyhydramnios
- oligohydramnios
- premature rupture of membranes
What is a common cause of polyhydramnios?
gestational DM
baby has foetal polyuria, which leads to polyhydramnios
What is oligohydramnios?
not enough amniotic fluid
indicates that foetus may be hypoperfused
can be identified by USS
Why does premature rupture of membranes occur?
usually an inflammatory response
if this occurs at 28wks, baby will be delivered premature
What types of hormones are active during pregnancy?
- placental steroids
- maternal steroids
- foetal steroids
- placental peptide hormones
At what gestational age, does placental steroidogenesis occur?
7-8 weeks
What effects does P have during pregnancy?
- decidualisation of the CL
- smooth muscle relaxation (uterine quiescence)
- mineralocorticoid effect (CVS changes)
- breast development
Why does P cause an increased maternal HR during pregnancy?
Progesterone has a similar biochemical structure to aldosterone
increased Na (and H2O) retention
increased HR
Where does oestrogen synthesis occur during pregnancy?
androgens produced in foetus
then maternal adrenals convert to oestrogen
placenta cannot make oestrogen on its own
What is the order of oestrogen potency?
most potent
E3 > E2 > E1
What is function of oestrogen during pregnancy?
- development of uterine hypertrophy
- metabolic changes (INS resistance caused by antagonism of insulin by E3)
- CVS changes
- breast changes
Which oestrogen molecules increase during pregnancy?
all of them
highest E2
then E3
then E1
[serum levels]
Which androgens are made by the adrenal glands during pregnancy?
made by both maternal and foetal adrenal glands
- dihydroandrosterone
- androstenedione
- testosterone
When do the main hormonal changes occur during pregnancy?
PLACENTAL CRH
increase from trimester 2 onwards
may be involved in labour initiation (beyond threshold)
CORTISOL
increase from trim 2 onwards
metabolic changed (INS resistance)
foetal lung maturity
hPL
similar to GH structure (differs by 1aa)
mediates INS resistance
some function in lactation
PROLACTIN
levels increase throughout pregnancy
activity suppressed by high oestrogen in utero
but after delivery, oestrogen falls and PRL can act
breast development for lactation e.g. colostrum
How do steroid binding protein levels change during pregnancy?
[albumin] in pregnancy drop due to maternal haemodilution
therefore, there are less available steroid binding hormones compared to circulating steroids (more are in the active free state)
