Pregnancy, birth and lactation Flashcards
What tissue is unique to the placenta?
Trophoblast, which forms a unique relationship with the maternal endometrium
What is the chorion?
Trophoblast plus extra-embryonic mesoderm; this forms the chorionic vesicle, including the placenta
What is the allantois?
Endoderm lining, mesodermal covering: forms bladder and urachus
What is the yolk sac?
Site of haematopoiesis in early pregnancy; development of gut; primordial germ cells
What is the amnion?
Cavity in which embryo lies
Main source of amniotic fluid in early pregnancy (later from urine, lungs, skin).
Describe the stages of placenta development (pre-villous to tertiary villi)
Previllous embryo: no villi; cytotrophoblast covered with syncytiotrophoblast
Primary villi: defined cytotrophoblastic projections, covered by syncytiotrophoblast
Secondary villi: mesenchymal core within the cytotrophoblast; syncytiotrophoblast on surface
Tertiary villi: mesenchyme invaded by fetal blood vessels, the capillaries form a convoluted knot with a terminal dilation, where blood flow is slower for increased exchange.
Describe what happens after tertiary villi form (placenta)
Formation of cytotrophoblastic shell, anchoring villi; substantial branching of villi
Migration of cytotrophoblast cells to maternal vessels, glands, myometrium
Describe a mature villi
‘Mature’ villi: very branched; outer syncytiotrophoblast; incomplete cytotrophoblast layer; fetal blood vessels contiguous with the syncytiotrophoblast; loose mesenchyme containing scattered phagocytes.
Describe the flow of blood in and out of the foetus
Placental intervillous spaces receive deoxygenated blood from branches of the umbilical arteries
Oxygenated, nutrient- rich venous blood from the placenta passes via an umbilical vein (left) to the foetal liver (through-passed by the ductus venosus) and from there to the right atrium.
What area of the placenta receives blood from umbilical arteries?
Intervillous spaces
How does oxygenated blood reach the foetal right atrium?
From umbilical vein (left) to the foetal liver (through-passed by the ductus venosus)
Where does maternal arterial blood enter placenta?
Intervillous spaces from the spiral arteries
What type of blood flow occurs in the intervillous spaces for maximal O2 exchange?
Countercurrent flow
How does blood leave the intervillous spaces?
Uterine veins
How do uterine contractions affect placental blood supply?
Uterine contractions allow blood to spurt in from the arteries, but close venous outflow, causing the low pressure in the intervillous space to rise.
When the myometrium relaxes, veins reopen and intervillous pressure falls.
How does placental efficiency increase in the latter weeks of pregnancy?
Branching of villi & formation of a brush border on the syncytiotrophoblast increases the surface area for exchange
A decrease in villous diameter from 140-200µm in early pregnancy to 40µm in late pregnancy
Thinning of the placental ‘barrier’
What makes up the placental ‘barrier’?
Endothelium and basal lamina of fetal capillary
Stroma of villus (not present in some areas of the late placenta)
Basal lamina of the cytotrophoblast
Syncytiotrophoblast: (thickness 10µm in early pregnancy, 1-2µm in late pregnancy).
What molecules can diffuse across the placental barrier?
Water, electrolytes, urea, cholesterol, gases
What molecules are transported across the placental barrier?
Immunoglobulins (IgGs which confer passive immunity to the fetus)
Concentrate substances in the foetal circulation: e.g. Fe, Ca, Cu, glucose, vitamin B12, folate, riboflavin, vitamin C, amino acids, some hormones
What is the role of hCG?
Preserve the corpus luteum
Continual production of progesterone and oestrogens until the foeto-placental unit takes over
What is the role of progesterone in maintaining pregnancy?
Maintaining uterine quiescence
What is the role of oestrogen in maintaining pregnancy?
Uterine growth
How do hormones convert maternal metabolism to the pregnant state?
hPL human placental lactogen, aka human chorionic somatomammotrophin (similar to GH & PRL).
Increases maternal lipid breakdown to provide the foetus with energy
What happens to levels of oestrogen and progesterone through pregnancy?
Slowly increase
What happens to the level of hCG through pregnancy?
Rises and peaks at the end of the first trimester, falls through 2nd trimester to a low level in the 3rd trimester
What are the oestrogens?
Oestrone, oestradiol and oestriol
What does the mother have to produce oestrogens BUT what does she lack the ability to do after what event?
Mother provides LDL cholesterol
She lacks enzymes to synthesise progesterone and oestrogens form cholesterol
AFTER the termination of the corpus luteum function at three months
Can the placenta produce progesterone and oestradiol from cholesterol?
Placenta can produce progesterone from cholesterol
BUT the primate placenta does not have the key enzymes necessary to produce estradiol from cholesterol
What are the enzymes needed to convert cholesterol to oestradiol?
17 alpha-hydroxylase and 17-20 lyase/ desmolase
What does the foetus use to convert cholesterol to oestradiol for the mother?
Weak androgen dehydroepiandrosterone (DHEA) which is synthesized in the foetal adrenal gland.
This is converted by the placenta in part to estradiol.
Where is dehydroepiandrosterone (DHEA) synthesised?
The foetal adrenal gland
How are estriol and estrone formed, what is required?
DHEA is 16-hydroxylated by the liver (16 alpha hydroxylase)
Yields a steroid which is converted by the placenta to estriol Some estrone is also formed.
What is a weak oestrogen which is the main oestrogen secreted in the urine?
Estriol
Why is it surprising that the foetus isn’t rejected?
Foetus and placenta express both PATERNAL and maternal genes
What five ways does the trophoblast avoid immune rejection?
Class 1 MHC of paternal origin are not expressed on the membrane of trophoblast cells in contact with the maternal blood.
Instead, the trophoblast expresses a specific HLA-G which interacts with maternal cells including uterine natural killer (uNK) cells to prevent rejection
The trophoblast secretes molecules which exert some inhibition of the immune response (hCG and progesterone)
Trophoblast produces an enzyme (IDO indoleamine 2,3-dioxygenase) that degrades tryptophan that is necessary for T-cell activation.
The uterine T cell population is shifted from Th1 (cell-mediated immunity) type to Th2 (antibody-mediated).
Describe the symptoms of pre-eclampsia
Very high arterial blood pressure which causes renal
damage (albumin appears in the urine) and oedema.
May lead to convulsions and death
What methods are used for pre-natal diagnosis?
Amniocentesis
Chorionic villus sampling
Ultrasonography
Describe amniocentesis
50-100ml of amniotic fluid is aspirated at 16-20 weeks pregnancy and foetal cells are cultured and karyotyped to check for chromosomal abnormalities, single gene disorders, and for alpha-fetoprotein, a sign of spina bifida.
Describe chorionic villus sampling
Small sample of cells (called chorionic villi) is taken from the placenta where it attaches to the wall of the uterus
Allows much earlier diagnosis of chromosomal abnormalities, single gene disorders and transplacental virus infection (eg. Rubella)
Risk of spontaneous abortion
Describe Ultrasonography
Ultrasound is a non-invasive, rapid technique that visualises the living foetus and placenta.
Used to determine the gender and number of foetuses, placental position, size and development of the foetus, heart rate, and major anomalies such as spina bifida, hydrocephalus, or anencephaly.
How do increasing levels of progesterone act on the uterus during pregnancy?
Induce quiescence in the muscle cells directly
Act on chorionic enzymes which prevent the accumulation of activating prostaglandins from reaching the myometrium
The prostaglandin produced before term is largely prostaglandin I which relaxes smooth muscle
Reducing the numbers of oxytocin receptors within the uterine muscle.
What is the role of oestradiol in preparing for parturition?
○ Oestradiol induces production of contractions associated proteins by the myometrium, stimulates production of oxytocin receptors; and increases the excitability of the myometrium.
What is the role of placental CRH in preparing for parturition?
Acts as a signal of readiness of parturition
What stimulates myometrial contractions and modifies the cervix for parturition?
○ Placental prostaglandins (PGE2 and PGF2) act in this way; (earlier in pregnancy the relaxant prostaglandin PGI2 predominates).
What is the role of oestradiol in stimulating lactation?
Development of the ductal system
What is the role of progesterone in stimulating lactation?
Development of the alveoli
What is the role of hPL in stimulating lactation?
Lactogenic action, developing the secretory potential of the breast alveoli
What suppresses lactation during pregnancy?
High levels of progesterone and estradiol.
What effect does oestradiol have on endometrial development?
Stimulates the proliferative phase of growth and triggers spiral artery development
What effect does progesterone have on endometrial development?
Stimulates its secretory phase
Is the uterus completely quiescent in pregnancy?
No, there are spontaneous, non expulsive contractions
Why are the pregnancy contractions non-expulsive?
Small in amplitude
Myometrial cells are not coupled
What did Liggins (NZ) notice?
Sheep eating the weed Veratrum californicum (inhibits the hypothalamus) failed to deliver their lambs on time - went grossly over term.
Why do sheep without hypothalamus go grossly overterm?
Pituitary would not secrete adrenocorticotropic hormone, ACTH; and the foetal adrenal would not secrete steroids.
What is the relationship between oestradiol and progesterone in early parturition (sheep model)?
Oestrogen increases myometrial sensitivity but also gives rise to a local increase in prostaglandin secretion which causes myometrial contractions.
Also an increase in oxytocin receptors and an increase in gap junctions between myometrial cells both of which enhance expulsive contractions.
Progesterone is thought to suppress this
How is progesterone signalling for parturition different in humans than sheep?
Progesterone does suppress myometrial contractions but human maternal plasma progesterone does not fall significantly at term
Rather, there is a change in the progesterone receptors from the type B receptor (which predominates during pregnancy and which inhibits production of contractile prostaglandins production (and stimulates their breakdown)) to a type A receptor (which stimulates production of contractile prostaglandins and inhibits their breakdown).
What is the difference in glucocorticoid injection in sheep and humans?
In humans, glucocorticoid injections do not elicit contractions but do facilitate the production of contractile prostaglandins
What is the type B progesterone receptor?
Type B receptor (which predominates during pregnancy and which inhibits production of contractile prostaglandins production (and stimulates their breakdown))
What is the type A progesterone receptor?
A receptor (which stimulates production of contractile prostaglandins and inhibits prostaglandin breakdown).
What happens to placental CRH levels as the mother nears partition?
Placental CRH levels rise toward term and CRH levels at 16-20 weeks roughly predict when a woman will give birth.
What happens to oxytocin secretion at term?
At term, the oxytocin cells in the hypothalamus also become coupled and can fire synchronously. Oxytocin receptors in the human myometrium also increase at term.
What are the roles of prostaglandins?
Soften the uterine cervix in addition to contracting the uterus.
What ensures the myometrial contractions proceed?
Positive feedback mechanisms
What is the Ferguson reflex?
Stretch of the cervix by the descending foetal head stimulates the ‘Ferguson reflex’ - sensory fibres in the cervix convey information about stretch via the spinal cord to the hypothalamus to stimulate the release of oxytocin.
Oxytocin receptors induced in the myometrium by oestrogens cause more contraction of the myometrium, thus creating a positive feedback loop.
How do contractions and stretch contribute to the prostaglandin synthesis?
Synthesis of more contractile prostaglandins creating a further loop
What breaks the positive feedback loops?
When the child is delivered
What are the three stages of birth?
- First stage: contractions cause the cervix to dilate so that the foetal head can pass. At the same time the amniotic sac usually ruptures (‘waters breaking’)
- Second stage: the child is delivered normally head first, and with the occiput facing anteriorly.
- Third stage: Delivery of the placenta. The uterus contracts very firmly to prevent excessive blood loss as the placenta is sheared from the wall of the uterus.
How is blood loss prevented by the body?
The uterus contracts very firmly
What drug is given to increase uterine contractions (to reduce blood loss)?
Ergometrine, a smooth muscle stimulant, is often administered to enhance this contraction.
Near the end of pregnancy what changes occur to prepare the foetus for postnatal life?
Production of surfactant in the lungs - to allow lung expansion when air is first breathed
Changes to gut and liver enzymes to allow the foetus to metabolize its post-natal milk diet.
What are the names of ‘milk’ glands?
Mammary gland
What do the ducts give rise to?
12-20 galactopoetic (milk-producing) lobules
What do the galactopoetic lobules empty into?
Common lactiferous duct
What stimulus leads to the maintenance of lactation?
Sucking stimulus
What hormone stimulates the synthesis and secretion of milk constituents?
Maternal pituitary prolactin
What mechanism facilitates the ejection of milk?
Contraction of the myo-epithelial cells which surround the alveoli
What stimulates the contraction of the myo-epithelial cells?
Oxytocin
What negatively controls prolactin release?
Dopamine
What does colostrum contain?
Abundance of IGA antibodies made by the mother and which readily pass across the neonatal gut epithelium.
Why does lactation prevent further pregnancy?
The suckling stimulus also alters GnRH output from the hypothalamus, reducing GnRH pulses. In this way, lactation suppresses ovulation and so prevents a further pregnancy which would create excessive metabolic demand on the mother.
What is the main role of oestrogens during the 2nd and 3rd trimester of pregnancy?
To stimulate the synthesis of oxytocin receptors and prostaglandins in uterine muscle
Which hormone protects against excessive maternal calcium (Ca ) loss during lactation?
Calcitonin
During pregnancy the placenta produces oestrogens from which secretion of the fetal adrenal…
Dihydroepiandrosterone
Structures through which oxygen is absorbed into the fetus
Placental villi
Which of the following contributes only to placental tissue?
Cytotrophoblast
How does the placenta develop?
Forms from the trophoblast as the cytotrophoblast develops increasing levels of villi invaginating into the syncytiotrophoblast. Vessels permiate the trophoblast to a greater extent.
What is the hormone secreted by the corpus luteum that causes the development of the endometrial layer of the uterus?
Progesterone
The mammary gland is situated primarily in
The superficial fascia
The main hormone that stimulates growth of mammary gland ducts
Oestradiol
The main hormone that stimulates growth of mammary gland alveoli
Progesterone
