Hormonal Coordination of Maternal Adaptations to Pregnancy Flashcards
1
Q
what is the hormone detected by home pregnancy kits, which can even be detected in low amounts
A
hCG
2
Q
what type of hormone is hCG
A
glycoprotein
3
Q
when does hCG synthesis begin and by what cells
A
- hCG synthesised by trophoblast cells in blastocysts, starting before implantation
4
Q
at what point in hCG synthesis can home pregnancy kits detect it
A
- hCG synthesis by trophoblasts in blastocyst before implantation
5
Q
as embryos begin to implant and early into pregnancy, what happens to hCG concentrations & why
A
- hCG concentrations rise quickly
- as hCG mostly synthesised by syncytiotrophoblast cells (specialised trophoblast cell soon after implantation)
6
Q
when do hCG concentrations peak
they decline gradually after this
A
around week 8-9 of pregnancy
7
Q
what is hCG critical for in body to recognise & why
A
- pregnancy recognition
- without, corpus luteum will regress -> lose progesterone production
8
Q
how does hCG maintain and promote progesterone synthesis that is essential to pregnancy
A
by binding to LHR on corpus luteum
(sim to LH hence why hCG can also trigger ovulation)
9
Q
what happens to corpus luteum without pregnancy
A
-no hCG -> regression of CL and loss of progesterone
- marking end of cycle where implantation has not occurred
- menstruation occurs (shedding of endometrium)
10
Q
what type of hormone is progesterone (P4)
A
- steroid hormone
- synthesied from LDL cholesterol
11
Q
what synthesises progesterone initially and later on
A
- initially / early pregnancy from luteal cells in corpus luteum (~wk 6/7/8 have drop in production from CL)
- later placental production becomes dominant
12
Q
key functions of progesterone
A
- promote implantation (decidualisation - preparing endometrium)
- maintains pregnancy
- drives maternal respiratory adaptations - increasing sensitivity of respiratory centre to O2
13
Q
how does progesterone maintain pregnancy (2)
A
- myometrial quiescence: suppress (myometrium) contractions
- [maternal] immune tolerance: to developing embryo
14
Q
how does progesterone promote implantation
A
- initiating changes in decidua (modified endometrium) making it receptive to implantation
15
Q
what hormone is essential for pregnancy
A
progesterone
16
Q
if woman not have corpus luteum during pregnancy eg/ IVF (since embryo implanted straight into uterus) what happens regarding progesterone for pregnancy
A
- supplemental progesterone used
- essential to establish and maintain pregnancy
17
Q
in addition to progesterone, human placenta makes multiple other what
A
steroid hormones
18
Q
what are some of the steroid hormones the human placenta makes
A
- oestrogens (including oestradiol)
19
Q
can human placenta make oestrogens by itself, if not, what is used?
A
- no
- some of the substrates for production of oestrogens by placenta are actually coming from the foetal adrenal (eg/ 19-C androgen precursors made in foetal adrenal)
20
Q
key functions of oestrogens in pregnancy
A
- vasodilators
- regulate placental progesterone production
- stimulate maternal RAS -> incr blood volume
- promote mammary development
- promote foetal adrenal steroid synthesis
21
Q
how does oestrogen function of vasodilator result in
A
- utero-placental blood system exposed to very high levels oestrogen coming from placenta
- oestrogens important for driving increase in blood flow thru uteroplacental bed
22
Q
how does oestrogen regulate placental progesterone production
A
- oestrogens increase expression of LDL receptor on placenta
- important for placenta to be able to take up LDL cholesterol
- which is the precursor for progesterone production
23
Q
how does oestrogen promote foetal adrenal steroid synthesis
A
- oestrogens stimulate LDL cholesterol production from foetal liver
- which is a substrate for many steroids produced by foetal adrenal (eg/ corticosteroids)
24
Q
why do corticosteroids need to increase in late pregnancy (produced by foetal adrenals)
A
important driver of foetal organ maturation
25
what synthesises growth hormone initially and later on
- initially anterior pituitary (drops to low later on alongisde placenta production)
- later on high placental production dominates
26
- key function of GH in pregnancy
- importance of this
- induces insulin resistance: shifts maternal metabolism to using lipids rather than glucose
- to preserve glucose for foetal supply
27
is the GH produced from placenta the same as anterior pituitary, what are the consequences?
- not same
- still binds to GH receptor (ie/ no consequence said)
28
in what way is GH released from anterior pituitary gland & when does this stop
- pulsatile
- most pulses lost by mid-pregnancy
29
- after pulses of GH lost around midpregnancy, what happens to GH levels, especially into late pregnancy
- what does this reflect
- very high GH concentration
- reflects production of GH from placenta
30
why does GH from pituitary gland fall during late human pregnancy
- GH coming from placenta -> negative feedback at hypothalamus & anterior pituitary -> suppress production GH from pituitary
31
can you definitely conclude what is happening in a human body with GH from mouse studies
no
32
which maternal adaptations during human pregnancy is GH important for
metabolic adaptations (feeding and digestive maternal adaptations)
33
what is a potential metabolic adaptation (incr food intake) that GH has on pregnancy as a key function of GH
- in mice
- GH acts on nerves in stomach -> downregulate nerve signals that signal stretch of stomach -> decreasing satiety signals => may allow increased food intake
34
where is placental lactogen (hPL) produced from
placenta (syncytiotrophoblast - specialised trophoblast cells of blastocyst)
35
key functions of placental lactogen
- promotes insulin secretion - by promoting beta cell expansion (through increased proliferation and reduced apoptosis), enhancing insulin release from beta cells (by increasing sensitivity of glucose sensors in beta cells)
- mammary gland development and function
- promote foetal growth by promoting IGF production
36
what is the increase of placental lactogen like throughout pregnancy
steadily increases
37
if a pregnancy is complicated with placental insufficiency, what would we expect placental lactogen levels to look like
low
38
how do placental lactogens act
- mostly binds to prolactin-receptor (PRL-R)
39
describe what it means to increase glucose sensors, in situation of increasing insulin secretions
- to increase insulin secretion in response to glucose
40
which 3 hormones are part of prolactin-growth hormone family (PRL-GH family)
- growth hormone (GH)
- placental lactogen (hPL)
- prolactin
41
where is prolactin made from
- pituitary
- but increased in pregnancy in response to oestrogens and progesterones
- decidua?
42
list 8 hormones that increase during pregnancy & (+1) help coordinate maternal adaptations to pregnancy
- human chorionic gonadotrophin (hCG)
- progesterone
- other steroid hormones: oestrogens
- growth hormone
- placental lactogen
- prolactin
- relaxin
- leptin
----
- insulin (not increase during pregnancy)
43
which 2 hormones mentioned does not come from placenta
prolactin
insulin
44
key functions of prolactin
- promotes insulin secretion - by promoting beta cell expansion (through increased proliferation and reduced apoptosis), enhances insulin release from beta cells (by increasing sensitivity of glucose sensors in beta cells)
- mammary gland development and function
- anti-inflammatory
45
which 2 hormones in prolactin-growth hormone family have similar key functions & why
- placental lactogen (hPL)
- prolactin
----
- because both are primarily binding to prolactin receptor
46
what has prolactin been seen to promote
- mammary gland ductal branching
- formation of alveoli
- promotion of milk protein production
47
what is the link between insulin and placenta
- placental signals have significant effects on insulin secretion and insulin sensitivity
48
which hormones mentioned induce insulin resistance
which hormones mentioned increase insulin secretion
- insulin resistance: growth hormone
- insulin secretion: placental lactogen (hPL), prolactin
49
when are increases in insulin secretion and decreases in insulin sensitivity / increased insulin resistance particularly seen in pregnancy based on hormone production time
- late pregnancy
50
at what other intermittent times during pregnancy does insulin secretion increase higher than what would be expected in non-pregnancy
MoA for this increase
- in response to glucose
- due to increase responsiveness of beta cells to glucose (hPL, prolactin)
51
decrease in insulin sensitivity could also be considered as what
increased insulin resistance
ie/ body's cells become less responsive to effects of insulin, leading to impaired glucose uptake and regulation
52
from what hormone and why is insulin resistance seen in pregnancy
- GH
- as a maternal metabolic adaptation
- to preserve glucose for foetal supply
53
what kind of protein is relaxin
protein hormone
54
what is chorion
outermost membrane surrounding embryo; contributes to placenta formation
55
what is relaxin coming from
corpus luteum
56
what pregnancy would result in no relaxin production
- anovulation pregnancies since no corpus luteum
57
when does relaxin release occur (which trimester), when does it fall, when does it stabilise
- relaxin production occurs in first trimester of pregnancy
- falls in second trimester and remains stabilised in third trimester
58
key functions of relaxin
- systemic vasodilator
- renal vasodilator
- cervical softening and ripening (MMM -> ECM remodeling)
59
due to the vasodilator key functions of relaxin, what effects do these have on the body (maternal adaptations)
- increased cardiac output & cardiovascular performance in pregnancy due to systemic vasodilaton
- increased renal function and increased renal blood flow due to renal vasodilation
60
MoA for relaxin result in cervical softening and ripening
- relaxins induce production of enzymes such as matrix metalloproteinases (MMM)
- (MMM can digest and remodel ECM)
=> extracellular matrix remodeling
- ECM remodeling important in timing of labour
61
in regards to relaxin causing cervical softening and ripening, if relaxin levels are elevated in early pregnancy -> would this be more likely to cause a preterm delivery, full-term delivery, late-term delivery
pre-term delivery
62
what type of hormone is leptin
protein hormone
63
what does leptin come from if not pregnant
- adipose tissue
64
generally, what does increase in leptin do to food intake appetite
- increase leptin -> reduced food intake appetite
65
where does leptin come from in pregnancy
- both adipose and placenta (syncytiotrophoblast cells)
- increased in response in BOTH to hCG and oestrogen (released in pregnancy)
66
when do levels of leptin peak in pregnancy
- second trimester / mid-pregnancy 24-28 weeks
67
explain what 2 pathways syncytiotrophoblasts in placenta are increasing leptin
- produce leptin
- express leptin receptor
68
what would explain the actions leptin has on the placenta (which produces leptin)
syncytiotrophoblasts in placenta expressing leptin receptor
69
functions of leptin
- in vitro: enhances placental nutrient transport, placental angiogenesis
- central leptin resistance in pregnancy: leptin does not reduce food intake in pregnancy
70
what is placental angiogenesis
- formation of blood vessels within placenta
- pivotal process
- establishes fetomaternal circulation
71
what about the formation of the placenta allows the link between mother and foetus in placental angiogenesis if its blood vessels within only placenta
-angiogenesis: formation of new blood vessels; involves branching of new microvessels from pre-existing larger blood vessels
- placenta is made up of maternal tissue and foetal tissue
- maternal blood enters placenta through maternal arteries in uterine wall
(placenta is attached to uterine wall)
- maternal arteries come in close contact to foetal blood vessels within placenta)
- foetal blood vessels in developing placenta initially not fully formed
- placental angiogenesis occurs which further develops foetal blood vessels closer to maternal blood supply for greater capacity of exchange through close proximity.
72
what do these key functions of hormones contribute to in pregnancy
maternal adaptations in pregnancy
73
in regards to leptin, what state is pregnancy in
state of leptin resistance
74
studies show that increased leptin levels in first trimester of humans had increased or decreased weight gain
increased weight gain
ie/ leptin resistance
