Lecture 6: Role of Placenta in DOHAD Flashcards
What is transported through the placenta via diffusion?
Oxygen, steroid hormones, fetal waste
What are the features of facilitated diffusion via the placenta?
No ATP required, glucose moves through GLUT transporters
What are the features of active transport through the placenta?
ATP required, transports amino acids, folate and micronutrients
What are the most important amino acid transporters?
System A
What are the features of vesicular transport across the placenta?
Captured by microvilli and transport immunoglobulins
What is the glucocorticoid barrier?
Provides a gradient of glucocorticoids from the mother to the foetus
What gene is expressed in the placenta to convert active glucocorticoids to inactive metabolites and why is this necessary?
11B-HSD2 - important to convert things to avoid them passing through the placenta
What does neurokinin B do?
Binds to phosphocholines – (used by parasites to evade the immune system)
What types of cells does the placenta inhibit?
Maternal T-cells (lymphatic suppressors)
What antibodies cross the placenta?
IgG antibodies - provide immunity for the foetus during early life
What are some endocrine roles of the placenta?
Regulate maternal insulin levels, increase BG and FA, secrete progesterone
What are the roles of leptin/ghrelin?
Peptide hormones regulating maternal hunger/appetite
When does implantation occur?
Day 7/8
What is implantation?
Free-floating blastocyst comes into contact with uterine lining and invades it. Trophoblast forms placenta and inner cell mass forms fetus.
What is placentation?
The development of specialised regions of fetal and maternal origin, when maternal and zygote cells come within close proximity
When is placentation complete in humans?
End of 1st trimester
What is placenta previa?
Occurs when placenta implants such that when it grows it covers the cervix, fetus has no passage to pass out through at childbirth - need hospital intervention for survival - require caesarean (1 in 200)
What is placenta accreta?
Placenta invades far beyond the depth of what is considered normal and grows through the uterus and can invade beyond the uterus to structures such as the bladder - natural delivery would result in a severe amount of blood (placenta coming out and tearing away surrounding organs) - typically happens when women refuse any hospital/medical intervention during childbirth. If there is only partial accreta there may just be scarring. Usually uterus is completely removed and there is infertility after this (3 in 1000)
What are the maternal layers that classify placentation?
Epitheliochorial, endotheliochorial, hemochorial
What are the features of epitheliochorial?
A number of layers between the maternal and fetal blood supply - mother and fetus both have complete capillary networks and connect at a complex tree (whales, ruminants)
What are the features of endotheliochorial?
Single layer between maternal and fetal blood supplies (carnivores) – one tree diminished
What are the features of hemochorial?
Fetal capillaries sit in bath of blood - dilated blood spaces rather than individual capillaries (high order primates and rodents)
How can the placenta be categorised by shape (what animals are these in)?
- Diffuse – horse, placenta covers entire fetus
- Multicotyledonary – sheep
- Zonary – cat/dog
- Discoid – human and mouse
What are the types of fetal layers on the placenta?
Syncitiotrophoblasts, cytotrophoblasts - Mono (human), di or trichorial (rodent)
What are the features of the rodent placenta?
- Labyrinth: site of nutrient interchange with maternal and fetal interaction
- More cell types with individual functions
- Junctional zone: involved in hormone production, specialised for endocrine function
What are the features of the human placenta?
- Maternal blood bathes in chorionic villi
- Villous: capillaries in maternal blood space to absorb nutrients
- Extravillous: maternal uterus that interacts with the developing placenta
- Vascular tree sits in pool of blood
What are the effects of famine on placental size?
- Babies were lighter, placentas had reduced SA and placental size more affected in boys
- Offspring had glucose intolerance, coronary heart disease, increased stress responsiveness and obesity
What is the importance of placental ratio?
- For any given fetal body weight there is an optimal placental weight
- If the placenta is more or less than 20% of the fetal weight it can be detrimental
- Too large – inefficient placenta
- Too small – poorly developed placenta
What happens if there is an increased placental ratio?
Increased; BP, coronary heart disease, glucose intolerance
What happens if there is a reduced placental ratio?
Increased coronary heart disease in men
What are the common placental adaptations to maternal perturbations?
- Impaired placental structure: altered SA for transport and nutrient supply
- Dysregulated nutrient transport: glucose, AA, lipids
- Impaired endocrine functions: IGF2, leptin, CRH (reduced IGF2 – reduced fetal size)
- Dysregulated placental barrier: increased passage of glucocorticoids – impaired organ development and increased risk of disease
How are IGF-2 levels different in male and female placentas and why is this?
IGF-2 in the placenta upregulated in males but not in females - placenta of male foetuses prioritise making fetus large and female placentas prioritise the limitation of later disease development
Which sex is more likely to up regulate glucocorticoid barrier?
Females
How does alcohol affect foetal development?
Upregulates glucocorticoid expression
How does hypoxia affect placenta in females?
Hypoxia reduces Hsd11b2 expression – female glucocorticoid barrier is impaired
