Lecture 6: Role of Placenta in DOHAD

Question 1

What is transported through the placenta via diffusion?

Answer 1

Oxygen, steroid hormones, fetal waste

Question 2

What are the features of facilitated diffusion via the placenta?

Answer 2

No ATP required, glucose moves through GLUT transporters

Question 3

What are the features of active transport through the placenta?

Answer 3

ATP required, transports amino acids, folate and micronutrients

Question 4

What are the most important amino acid transporters?

Answer 4

System A

Question 5

What are the features of vesicular transport across the placenta?

Answer 5

Captured by microvilli and transport immunoglobulins

Question 6

What is the glucocorticoid barrier?

Answer 6

Provides a gradient of glucocorticoids from the mother to the foetus

Question 7

What gene is expressed in the placenta to convert active glucocorticoids to inactive metabolites and why is this necessary?

Answer 7

11B-HSD2 - important to convert things to avoid them passing through the placenta

Question 8

What does neurokinin B do?

Answer 8

Binds to phosphocholines – (used by parasites to evade the immune system)

Question 9

What types of cells does the placenta inhibit?

Answer 9

Maternal T-cells (lymphatic suppressors)

Question 10

What antibodies cross the placenta?

Answer 10

IgG antibodies - provide immunity for the foetus during early life

Question 11

What are some endocrine roles of the placenta?

Answer 11

Regulate maternal insulin levels, increase BG and FA, secrete progesterone

Question 12

What are the roles of leptin/ghrelin?

Answer 12

Peptide hormones regulating maternal hunger/appetite

Question 13

When does implantation occur?

Answer 13

Day 7/8

Question 14

What is implantation?

Answer 14

Free-floating blastocyst comes into contact with uterine lining and invades it. Trophoblast forms placenta and inner cell mass forms fetus.

Question 15

What is placentation?

Answer 15

The development of specialised regions of fetal and maternal origin, when maternal and zygote cells come within close proximity

Question 16

When is placentation complete in humans?

Answer 16

End of 1st trimester

Question 17

What is placenta previa?

Answer 17

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)

Question 18

What is placenta accreta?

Answer 18

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)

Question 19

What are the maternal layers that classify placentation?

Answer 19

Epitheliochorial, endotheliochorial, hemochorial

Question 20

What are the features of epitheliochorial?

Answer 20

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)

Question 21

What are the features of endotheliochorial?

Answer 21

Single layer between maternal and fetal blood supplies (carnivores) – one tree diminished

Question 22

What are the features of hemochorial?

Answer 22

Fetal capillaries sit in bath of blood - dilated blood spaces rather than individual capillaries (high order primates and rodents)

Question 23

How can the placenta be categorised by shape (what animals are these in)?

Answer 23

• Diffuse – horse, placenta covers entire fetus
• Multicotyledonary – sheep
• Zonary – cat/dog
• Discoid – human and mouse

Question 24

What are the types of fetal layers on the placenta?

Answer 24

Syncitiotrophoblasts, cytotrophoblasts - Mono (human), di or trichorial (rodent)

Question 25

What are the features of the rodent placenta?

Answer 25

- 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

Question 26

What are the features of the human placenta?

Answer 26

- 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

Question 27

What are the effects of famine on placental size?

Answer 27

* 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

Question 28

What is the importance of placental ratio?

Answer 28

* 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

Question 29

What happens if there is an increased placental ratio?

Answer 29

Increased; BP, coronary heart disease, glucose intolerance

Question 30

What happens if there is a reduced placental ratio?

Answer 30

Increased coronary heart disease in men

Question 31

What are the common placental adaptations to maternal perturbations?

Answer 31

* 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

Question 32

How are IGF-2 levels different in male and female placentas and why is this?

Answer 32

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

Question 33

Which sex is more likely to up regulate glucocorticoid barrier?

Answer 33

Females

Question 34

How does alcohol affect foetal development?

Answer 34

Upregulates glucocorticoid expression

Question 35

How does hypoxia affect placenta in females?

Answer 35

Hypoxia reduces Hsd11b2 expression – female glucocorticoid barrier is impaired