describe the process of gastrulation; when does it occur?
day 15/16 PF
conversion of bilaminar disc (epiblasts and hypoblasts) to 3 germ layers (endoderm, mesoderm, ectoderm)
epiblasts migrate through the primitive streak, proliferate and differentiate into mesoderm
epiblasts -> endoderm
hypoblasts -> ectoderm
what tissues do the 3 germ layers develop into
endoderm: gut, liver, lungs
mesoderm: skeleton, muscle, kidney, heart, blood
ectoderm: skin, nervous system
male urogenital system development (4)
- Mesonephric ducts (Wolffian) → MALE genital ducts (SRY+)
- Leydig cells → testosterone → mesonephric duct growth
hCG peak week 8 after LMP → testosterone from developing testis (critical stage of development) - Testosterone → DHT → prostate, penis, scrotum
- Sertoli → AMH → regression of paramesonephric (Mullerian) ducts
female urogenital system development (4)
- Absence of SRY → ovary
- No testosterone → regression of mesonephric ducts
- No AMH → Mullerian duct persistence → oviducts, uterus, upper 1/3 of vagina
- Urogenital sinus → lower 2/3 of vagina
changes in heart at birth (2)
- Loss of foramen ovale (shunt between R & L atria)
- Loss of ductus arteriosus (connecting pulmonary artery & descending aorta)
→ allows use of pulmonary circulation
stages of lung development (6)
- Embryonic: lays down basic structure of lungs
- Pseudoglandular: develops gland-like structures
- Canalicular: becomes more elaborate
- Saccular: develops sacs
- Alveolar: sacs form alveoli (very late, around time of birth)
- After birth, changes continue and accelerate
surfactant
- function
- produced where?
- associated disease
- management
- important for low surface tension of alveoli → allows expansion of alveoli
- produced by type II pneumocytes
- Late surfactant production → respiratory distress syndrome: collapsed alveoli → insufficient oxygen
- Surfactant production increases w time ∴ can treat RDS by delayed delivery + allowing lungs to continue developing
OR give glucocorticoids / artificial surfactant
achondroplasia
FGFR3: gain of function mutation → loss of elongation of long bones in limbs
how does thalidomide cause maldevelopment
thalidomide → derangement of development of blood vessels in limb buds, especially upper → loss of nutrient supply → cell death
fetal membranes (3)
- decidua: endometrial origin
- chorion: cytotrophoblast (villous origin)
- amnion: epithelial layer & stroma of matrix and a few cells (including reticular layer)
basement ECM (of amnion layer) gives fetal membranes strength; holds amniotic fluid in place and prevents leakage
functions of the placenta (5)
SEBIC:
- separation: of maternal and fetal blood
- exchange: of metabolites, glucose, oxygen, amino acids etc. by facilitated diffusion, active transport, receptor-mediated etc.
- biosynthesis: hormones, growth factors, cytokines
- immunoregulation: immunological barrier between mother and fetus (limited passage of immune cells)
- connection: placenta anchors into maternal decidualised endometrium
placenta: villous development (5)
- Primary villous: cytotrophoblasts grow through syncytium
- Secondary villous: mesenchyme also invades
- Tertiary villous: cytotrophoblast layer becomes discontinuous, development of blood vessels
- When cytotrophoblast column reaches decidua, proliferates sideways to form trophoblastic shell
- Villous tree becomes progressively more elaborate; ↑branching → ↑SA for exchange
remodelling of spiral arteries
Remodelling necessary to meet demands of growing conceptus
1. Cytotrophoblasts plug spiral artery
2. Invasion of extravillous cytotrophoblast cells
3. Loss of vascular endothelium & smooth muscle cells → wide bore vessel that cannot vasoconstrict ∴ high blood flow, low pressure
Remodelling process involves NK cells, MMPs, TIMPs
Progresses to inner third of myometrium (as dedidual tissue has thinned)
4. Loss of cytotrophoblast plugs → exposure of placenta to full maternal blood flow
Late first trimester; pregnancy losses at this time: high pressure can detach conceptus from its implantation
growth factor families important for maternal-placental crosstalk + functions (4)
- IGFs & IGF-binding protein-1: IGF-II binds to type A insulin receptor → enhanced cytotrophoblast survival
IGFBP-1 increased in pregnancy → excess capacity for carrying IGFs - VEGFs, PDGF, PlGF:
in early pregnancy (low oxygen levels), VEGFs → formation of blood vessels
in last month of pregnancy, PlGF → capillaries ↑size and become closer to edges of villi → ↑transport - CSF-1 / M-CSF (colony-stimulating factors): roles in human placentation unclear
- TGFbeta: generally produced by decidua, inhibit trophoblast invasion and MMP activity in vitro
when does implantation occur
day 7 PF
