Pregnancy, Parturition and Late Fetal Development

Question 1

First trimester Fetal growth

Answer 1

Limited as nutrition is histiotrophic - reliant on uterine gland secretion and breakdown of endometrial tissues

Question 2

Second trimester Fetal growth

Answer 2

Switch to haemotrophic support at start of second semester
Achieved through haemochorial type placenta where maternal blood directly contacts the fetal membranes around 12 weeks gestation

Question 3

Primary chorionic villi

Answer 3

Cytotrophoblasts form finger like projections through syncytiotrophoblast layer into maternal endometrium

Question 4

Oxygen exchange across placenta

Answer 4

Diffusion gradient (high maternal O2 tension, low Fetal O2 tension)

Question 5

Glucose exchange across placenta

Answer 5

Facilitated diffusion by transporters on maternal side and Fetal trophoblast cells

Question 6

Water exchange across placenta

Answer 6

Placenta main site of exchange though some crosses amnion-chorion. Majority by diffusion, though some local hydrostatic gradients

Question 7

Fetal expulsion

Answer 7

Head engages with pelvic space 34-38 weeks
Pressure on fetus causes chin to press against chest
Fetus rotates so belly is to mother’s spine
Head expelled first after cervix dilation
Shoulders delivered subsequently followed by torso

Question 8

Origins of placenta

Answer 8

Amniotic cells begin to secrete into amniotic sac causing formation and expansion
Chorion - outer membrane surrounding conceptus unit
Connecting stalk - links developing embryo unit to chorion - begins to develop
Trophoblastic lacunae - large space filled with maternal blood formed by breakdown of maternal capillaries and uterine glands - become intervillous spaces aka maternal blood spaces

Question 9

Fetal membranes

Answer 9

Extraembryonic tissues that form tough but flexible sac, encapsulates fetus and forms basis of maternal-fetal interface

Amnion (inner) forms closed, avascular sac with developing embryo at one end and secretes amniotic fluid from 5th week - forms fluid filled sac that encapsulates and protects fetus

Chorion (outer) highly vascularised, gives rise to chorionic villi which is an outgrowth of cytotrophoblast from chorion that form the basis of Fetal side of placenta

Allantois- outgrowth of yolk sac, grows along connecting stalk from embryo to chorion and becomes coated in mesoderm and vascularises to form umbilical cord

Question 10

Chorionic villi

Answer 10

Provide substantial surface area for exchange
Undergo branching
Three phases of chorionic villi development
Primary - outgrowth of cytotrophoblast and branching of these extensions
Secondary - growth of Fetal mesoderm into primary villi
Tertiary - growth of umbilical artery and umbilical vein into the villus mesoderm, providing Vasculature

Question 11

Terminal chorionic villus

Answer 11

Convoluted knot of vessels and vessel dilation
Slows blood flow enabling exchange between maternal and Fetal blood
Whole structure covered in trophoblast

150-200 micrometer in diameter and 10 micrometers trophoblast thickness in early pregnancy
40 micrometers and 1-2 micrometer in late pregnancy

Question 12

Maternal blood supply to endometrium

Answer 12

Uterine artery branch into arcuate artery in myometrium which turn into radial arteries and then basal arteries in the endometrium which also turn to spiral arteries

Question 13

Spiral artery remodelling

Answer 13

Extra-villus trophoblast cells coating the villi invade down into maternal spiral arteries, forming endovascular EVT
Endothelium and smooth muscle is broken down - EVT coats inside of vessel
Conversion - turns spiral artery into low pressure high capacity conduit for maternal blood flow

Question 14

Electrolyte exchange across placenta

Answer 14

Large traffic of sodium and other electrolytes across placenta - combination of diffusion and active-energy dependent co-transport

Question 15

Calcium exchange across placenta

Answer 15

Actively transported against concentration gradient by magnesium ATPase calcium pump

Question 16

Amino acid exchange across placenta

Answer 16

Reduced maternal urea excretion and active transport of amino acids to fetus

Question 17

Maternal changes

Answer 17

Maternal cardiac output increases 30% during first trimester
Maternal peripheral resistance decreases up to 30%
Maternal blood volume increases to 40%
Pulmonary ventilation increases 40%

Question 18

Placenta and fetus oxygen exchange

Answer 18

Placenta consumes 40-60% glucose and O2 supplied
O2 content and saturation are similar to maternal blood
Embryonic and fetal hemoglobins have greater affinity for O2 than maternal

Question 19

Circulatory system maturation

Answer 19

Placenta acts as site of gas exchange
Ventricles act in parallel rather than series
Vascular shunts bypass pulmonary and hepatic circulation > close at birth

Question 20

Respiratory system maturation

Answer 20

Primitive air sacs form in lungs around 20 weeks, vascularisation from 28 weeks
Surfactant production starts around 20 weeks, unregulated towards term
Fetus spends 1-4hours/day making rapid respiratory movements during REM sleep

Question 21

GI system maturation

Answer 21

Endocrine pancreas functional from start of 2T, insulin from mid-2T
Liver glycogen progressively deposited - accelerated towards term
Large amounts of amniotic fluid swallowed - debris and bile acids form meconium

Question 22

Nervous system maturation

Answer 22

Fetal movements begin late 1T, detectable by mother from ~14 weeks (2T)
Stress responses from 18 weeks, thalamus-cortex connections form by 24 weeks
Fetus does not show conscious wakefulness- mostly in slow-wave or REM sleep

Question 23

System development changes

Answer 23

Orchestrated by Fetal corticosteroids
Surfactant production and liver glycogen both occur in parallel with corticosteroids

Question 24

Labour

Answer 24

Safe expulsion of fetus at correct time
Expulsion of placenta and Fetal membrane
Resolution/healing to permit future reproductive events
Pro-inflammatory reactions - immune cell infiltration and inflammatory cytokines and prostaglandin secretion

Question 25

Phases of labour

Answer 25

Phase 1 - quiescence - prelude to parturition - contractile unresponsive, cervical softening Phase 2 - activation - preparation for labour - uterine preparedness for labour, cervical ripening Phase 3 - stimulation - process of labour - uterine contraction, cervical dilation, Fetal and placenta expulsion Phase 4 - involution - parturient recovery - uterine involution, cervical repair, breast feeding

Question 26

Stages of labour

Answer 26

First stage -contractions start and cervix dilation -latent phase - slow dilation of cervix to 2-3 cm -active phase - rapid dilation of cervix to 10 cm Second stage -delivery of fetus -commences at full dilation of cervix -maximal myometrial contractions Third stage -delivery of placenta -expulsion of placenta and Fetal membranes -post-partum repair

Question 27

Remodelling of cervix

Answer 27

Critical role in retaining foetus in uterus High connective tissue content -provides rigidity -stretch resistant Bundles of collagen fibres embedded in proteoglycan matrix Changes to collagen bundle structure underlie softening, but mechanism unclear

Question 28

Stage of remodelling cervix

Answer 28

Softening - first trimester - measurable changes in compliance but retains cervical competence Ripening - weeks and days before birth - monocyte infiltration and IL6 and IL8 secretion, hylaluron deposition Dilation - increased elasticity - increased hyaluronidase expression - HA breakdown, MMPs decrease collagen content Post-partum repair - recovery of tissue integrity and competency

Question 29

Corticotrophin releasing hormone and initiation of labour

Answer 29

Fetus determines timing of parturition through changes in Fetal HPA axis CRH level rises exponentially towards end of pregnancy Decline in CRH binding protein levels, so CRH bioavailability increases

Question 30

CRH functions in labour

Answer 30

Promotes ACTH and cortisol release Increasing cortisol drives placental production of CRH - positive feedback Stimulates DHEAS production by Fetal adrenal cortex - substrate for estrogen production

Question 31

Estrogen and progesterone at labour

Answer 31

High progesterone through pregnancy maintains uterine relaxation As term approaches, switch from PR-A isoforms (activating) to PR-B and PR-C (repressive) isoforms in uterus - functional progesterone withdrawal Rise in estrogen receptor alpha expression Uterus becomes blinded to progesterone action and sensitised to estrogen action Lead to local changes in E:P ratio in uterine tissue

Question 32

Oxytocin

Answer 32

Nonapeptide hormone synthesised mainly in uterine-placental tissues and pituitary -uterine oxytocin production increases sharply at onset of labour -expression increase is driven by increase in estrogen levels -release promoted by stretch receptors - Ferguson reflex -signals through G-coupled oxytocin receptor (OXTR) -rise in estrogen promotes large increase in uterine OXTR expression

Question 33

Ferguson reflex

Answer 33

As fetus starts to bear down on cervix, stretch receptors in cervix and in vagina signal up to hypothalamus and firing of hypothalamus onto posterior pituitary triggers release of oxytocin into maternal circulation where it can act back on uterus and myometrium

Question 34

Oxytocin functions

Answer 34

Increase connectivity of myocytes in myometrium (syncytium) Destabilise membrane potentials to lower threshold for contraction Enhance liberation of intracellular Ca2+ ion stores

Question 35

Prostaglandins

Answer 35

Rising estrogen levels drive prostaglandin action in uterus -rising estrogen activates phospholipase A2 enzyme, generating more arachidonic acid for PG synthesis -estrogen stimulation of oxytocin receptor expression promotes PG release -peptide hormone relaxin and nitric oxide implicated in cervix remodelling

Question 36

Primary prostaglandins

Answer 36

PGE2 - cervix remodelling - promotes leukocyte infiltration into cervix, IL8 release and collagen bundle remodelling PGF2alpha - myometrial contraction - destabilises membrane potential and promotes connectivity of myocytes (with oxytocin) PGI2 - myometrium - promotes myometrial smooth muscle relaxation and relaxation of lower uterine segment

Question 37

Regulation of labour

Answer 37

Production of CRH by Fetal pituitary acts on Fetal adrenal to produce cortisol Cortisol is transferred to placenta for more production of CRH - positive feedback loop CRH acting on adrenal also promotes production of DHEAS, which in placenta is converted to oestrogen Oestrogen acts on myometrium promoting the expression of oxytocin receptor so uterus becomes sensitive to pituitary production of maternal oxytocin and that triggers contractions Oestrogen also promotes oxytocin production which stimulates contraction and promote prostaglandin production, which go on to stimulate more vigorous contractions In non labour state progesterone inhibits production of oxytocin receptors to keep myometrium quiescent

Question 38

Myometrial contractions

Answer 38

Contraction starts at Fundus, spread down upper segment Muscle contractions are brachystatic - fibres do not return to full length on relaxation Causes lower segments and cervix to be pulled up forming birth canal

Question 39

Placental expulsion

Answer 39

Rapid shrinkage of uterus after Fetal delivery causes area of contact of placenta with endometrium to shrink Uterine shrinkage also causes folding of Fetal membranes - peel off endometrium Clamping of umbilical cord after birth stops Fetal blood flow to placenta - villi collapse Haematoma formation between decidua and placenta Contractions expel placenta and Fetal tissue

Question 40

Placental repair

Answer 40

Uterus remains contracted after to facilitate uterine vessel thrombosis Uterine involution and cervix repair resorted non-pregnant state -shielding uterus from commensural bacteria -restore endometrial cyclicity in response to hormones