Placentation Flashcards
What does the inner cell mass differentiate into?
- Epiblast
2. Hypoblast
What is the epiblast?
Contacts the trophoblast
Gives rise to the three primary germ layers during gastrulation
Extends to form the amnion over the dorsal surfaces of the germ disc
What is the hypoblast?
Faces the blastocoel
Forms the primary yolk sac
Gives rise to extra-embryonic mesoderm
Where does extra-embryonic mesoderm come from?
Hypoblast
What does extra-embryonic mesoderm give rise to?
- Chorion
2. Cell layer that covers outside of yolk sac and amnion
What is the extra-embryonic coelom?
The space between the chorion and the amnion
How does the secondary yolk sac arise?
The primary yolk sac pinches off
What is the connecting stalk?
Connects the conceptus to the chorion
Future umbilical cord
What happens to the extra-embryonic coelom?
Obliterated at 12 weeks
Amnion pushed against inner surface of chorion
Where is the first site of haematopoiesis?
Yolk sac
What is exchanged between the mother and the yolk sac?
- Amino acids
2. Other nutrients
How does maternal-fetal exchange take place with the yolk sac?
Nutrients transported across chorion into fluid in the coelom, which bathes the yolk sac
What are the properties of the outer surface of the yolk sac?
- Absorptive epithelium
- GLUT1 and other transporters
- Synthesises many proteins like alpha-fetoprotein
What are the eight functions of the placenta?
- Gas transfer
- Excretion
- Immune
- Metabolic functions
- Synthetic functions
- Catabolic and resorptive functions
- Secretory functions
- Haematopoiesis
Where is the chorionic plate of the placenta?
Faces the fetus
Where is the basal plate of the placenta?
Apposed to decidua basalis
Where maternal blood enters
What is haemochorial placentation?
Maternal blood comes in direct contact with fetal chorion
Fetal villous trees arise from the chorionic plate and are bathed directly in maternal blood circulating in the intervillous space
Where are fetal capillaries located in the placenta?
Inside the villi
What does the trophoblast differentiate into?
- Syncytiotrophoblast
2. Cytotrophoblast
How is the syncytiotrophoblast formed?
Non-proliferative
Generated by continual fusion of cytotrophoblast cells
What is the structure of the syncytiotrophoblast?
Erodes into decidua
Breaks into endometrial glands and decidual capillaries
Spaces appear and coalesce to form lacunae
What fills the lacunae of the syncytiotrophoblast?
- Maternal blood
2. Glandular secretions
How are the earliest placental villi formed?
Cytotrophoblast cells and extraembryonic mesoderm penetrate into the trabeculae between the lacunae of the syncytiotrophoblast
Vascular network develops in the mesoderm and connects back to the fetus through the connecting stalk
How is the placental villus tree formed?
Repeated branching of the early villus
What is the intervillous space?
The lacunae once the villus tree forms
What is the stem villus?
Extends from chorionic plate
What is the anchoring villus?
Attached to basal plate
What are the side branches of the villi?
Intermediate villi from which terminal villi arise
When are terminal villi formed?
Second half of gestation
Where do placental villi form?
Initially, all over chorionic sac
Then, regress over superficial pole to leave discoid placenta
What does the rest of the chorionic sac form?
Placental membranes
Rupture at birth
When is maternal arterial circulation established?
10-12 weeks
What is histiotrophic nutrition?
Uptake of oviductal/uterine secretions by trophoblast or yolk sac
What is haemotrophic nutrition?
Nutrient, waste and gas exchange between maternal and fetal circulations
What is the principal source of nutrients in early pregnancy?
Carbohydrate and lipid-rich secretions from endometrial glands
What are endometrial glands stimulated by?
- Progesterone from corpus luteum
2. Signals from trophoblast
What protects the embryo from teratogenesis in embryogenesis?
Low oxygen environment
Protects from teratogenesis due to reactive oxygen species
Low oxygen favours fetal and placental stem cells
What is the embryonic period?
When most major organ systems are differentiating
First trimester
What is the fetal period?
Major growth period
Second and third trimesters
When is the switch from histiotrophic to haemotrophic nutrition?
First –> second trimester
Embryonic –> fetal period
At which stage of development is the fetus most sensitive to congenital malformations?
Embryonic phase
3 - 8 weeks
What is the surface area of the fetal villous tree?
12 - 14 m^2
What forms the uterine blood supply?
Arterial arcade formed by uterine and ovarian arteries in lateral walls of uterus, gives rise to arcuate arteries that encircle the uterus
What are the spiral arteries?
Arise from arcuate arteries
Supply blood to endometrium
Highly coiled, allowing for extension as uterus expands
Which arteries supply the placenta?
Spiral arteries
Muscular walls
What is involved in the conversion of spiral arteries during pregnancy?
- Endometrium invaded by extravillous trophoblast
- Loss of smooth muscle and endothelial lining in spiral arteries
- Vessel dilatation and loss of vasoreactivity
- Slows rate of inflow and reduces pressure
What condition is associated with failure of conversion of the spiral arteries?
Pre-eclampsia
What replaces the smooth muscle in converted spiral arteries?
Fibrinoid tissue
How are villi arranged in the placenta?
Lobules
How does the syncytiotrophoblast layer escape immune recognition?
Does not express MHC I or II antigens
What are the cells of the maternal immune system?
- Macrophages
- Lymphocytes
- Uterine natural killer cells
What causes placental stress?
Abnormal interaction between trophoblast and maternal immune cells leads to deficient conversion of spiral arteries so uterine malperfusion
What causes intrauterine growth restriction?
- Poor placental development
2. Poor placental function
What does effective placental exchange require?
- Stable low-pressure, high-volume maternal blood supply
- Large surface area
- Transporter mechanisms for large or hydrophilic molecules
- High transplacental gradient
How does the villous become specialised locally?
- Thick regions for hormone synthesis
2. Thin vasculosyncytial regions for diffusional exchange
How much oxygen does the placenta use?
30% of total O2 used by feto-placental unit
What causes the double Bohr shift in the placenta?
- Loss of CO2 from fetal blood increases pH and O2 binding
2. Gain of CO2 by maternal blood reduces pH and O2 binding
What is the pO2 in the uterine artery?
90mmHg
What is the pO2 in the uterine vein?
45mmHg
What is the pO2 in the umbilical vein?
30mmHg
What is the pO2 in the umbilical artery?
20mmHg
How do materials pass across the placenta?
- Passive diffusion
- Facilitated diffusion
- Active transport
- Endocytosis
What is transported across the placenta by passive diffusion?
- Gases
- Free fatty acids
- Urea
What is transported across the placenta by facilitated diffusion?
- Glucose
2. Free fatty acids
What is transported across the placenta by active transport?
Amino acids
Which proteins facilitate glucose transport?
GLUT proteins
Where is GLUT1 expressed?
Apical membrane of syncytiotrophoblast
Microvilli
Why are amino acids transported by active transport?
Fetal:maternal plasma ration is greater than 1 so going against gradient
What are the three main amino acid carrier systems?
- Systems A and AC
- System XAG
- System L
What do systems A and AC carry?
Neutral amino acids
Alanine, glycine
Na+-dependent
What does system XAG carry?
Acidic amino acids
Glutamic acid, aspartic acid
Na+-dependent
What does system L carry?
Neutral amino acids
Leucine, phenylalanine
Na+-independent
What is carried by receptor-mediated endocytosis in the placenta?
IgG antibodies
When are IgG antibodies transported?
Third trimester of pregnancy
How is IgG transported?
Binds to receptors on microvillus membrane
Concentrated in coated pits at base of microvillus
How is maternal metabolism modulated?
Placental hormones
What happens to maternal metabolism in early pregnancy?
- Appetite stimulated
2. Deposition of nutrient resources
What happens to maternal metabolism in later pregnancy?
- Resources mobilised for transfer to fetus
2. Mobilised for use in lactation
Where does hCG act?
LH receptors in corpus luteum
Where is hCG synthesised?
Syncytiotrophoblast
What is the role of hCG?
Maintain corpus luteum so that it continues producing progesterone until the placenta takes over
What is the structure of hCG?
Glycoprotein with two non-covalently linked subunits
Alpha subunit identical to LH, FSH and TSH
Beta subunit unique but very similar to LH
What is hPL?
Human placental lactogen
- Appetite stimulant
- Stimulates lipolysis and raises maternal FFAs
- Induces growth and differentiation of mammary glandular tissues
Where is hPL synthesised?
Syncytiotrophoblast
How do hPL levels change throughout pregnancy?
Synthesis begins at 10 weeks
Continues to rise until birth
What is the function of placental growth hormone?
- Stimulates lipolysis
- Stimulates gluconeogenesis
- Regulates maternal IGF1 levels and insulin sensitivity
- Elevates maternal glucose levels - glucose intolerance
- Suppresses maternal growth hormone secretion
Where is placental growth hormone synthesised?
Syncytiotrophoblast
What is the role of leptin?
- Appetite stimulant
2. Stimulates expression of placental transporter proteins
How does maternal sensitivity to leptin change in pregnancy?
Peripheral leptin resistance allows mother to lay down adipose reserves
Where is leptin synthesised?
Syncytium
Which hormones regulate leptin?
- Oestrogen
2. hCG
When do leptin levels peak?
End of 2nd/start of 3rd trimester
What is PAPP-A?
Pregnancy associated protein A
Protease that cleaves IGF proteins to increase their bioavailability
How do PAPP-A levels change throughout pregnancy?
Rise continuously
What is the role of progesterone in pregnancy?
- Maintains uterine quiescence
- Stimulates endometrial glands
- Appetite stimulant
- Immunomodulatory
Where is progesterone synthesised in pregnancy?
Syncytiotrophoblast of placenta
What is progesterone synthesised from?
Cholesterol taken up from apical surface of placenta
What occurs to steroid hormones in the fetus?
- Conjugates steroid hormones in liver or adrenal gland to inactivate them and protect the fetus from masculinisation
- Placenta de-sulphates them and converts them to oestrogens and secretes them into maternal circulation
What do oestriol levels indicate?
Fetal well-being
Indication of fetal liver function
What allows the fetal HPA axis to mature in isolation?
11ß-hydroxysteroid dehydrogenase metabolises maternal cortisol to inactive cortisone
What is maternal microchimerism?
Male cells found in female thyroid tissue after pregnancy
May be responsible for autoimmune diseases
May be repair
What kind of fetal DNA is found in the maternal circulation?
Fetal cell-free DNA and RNA
10% of circulating DNA
Short fragments
