Lecture 13: Placenta/pregnancy

Question 1

Human Chorionic gonadotrophin (hCG) features?

Answer 1

Is two chain with TSH, LH and FSH all sharing the same alpha chain but having different Beta chains that provide their specificity.

bhCG is produced by the syncytiotrophobalst of the preimplantation blastocyst and placenta and is detectable in the maternal blood/urine within days of impantation.

Twins result in increased hCG as it’s levels are proportional to the amount of syncytiotrophoblast. Misscarriage is seen by this not increasing.

Question 2

Functions of hCG?

Answer 2

1. hCG binds to the LH/hCG receptor and thus transmits similar dignals to LH
2. Luteal support - important in the production of progesterone and oestrogen by the ovary during the first 6-8 weeks of pregnancy. Stopping the regression of the corpus luteum.
3. The CL doubles in size in about a month into pregnancy under the influence of hCG.
4. After this time the placenta take over progesterone production.
5. Responsible for preventing the uterus returning to the normal cycle by causing sustained P and E secretion by CL

Question 3

hCG role in male fetuses?

Answer 3

hCG synthesised from the mothers blood has an LH-like activity that stimulate testosterone synthesis by the leydig cells of the testes before the pituitary can pump out large enough quantities of LH.

Question 4

Progesterone synthesis?

Answer 4

Progesterone is produced by the STB of the placenta and removal of the ovaries doesn’t compromise human pregnancy after 6-8 weeks.

Trophoblasts can not synthesis progesteron from acetate but rather from LDL-cholesterol derived from the mothers blood uptaken by various receptors expressed on STB.

Question 5

Functions of Progesterone?

Answer 5

Progesterone maintains uterine quiescence

Along with oestrogen, progesterone converts the uterine environment to one that is conductive to pregnancy.

Progesterone receptors are expressed by both glands and stromal cells in the endometrium/decidua

Question 6

Oestrogen production in pregnancy?

Answer 6

There is a 1000 fold increase in oestrogen during pregnancy - made by the feto-placental unit. Human placenta has no 17a hydroxylase so can not produce oestrogen de novo.

The placenta can aromatise testosterone, androstenedione and dehydroepiandrostene to estrogen and estradiol.

These precursors are made in the fetal adrenals and transported to the placenta for aromatisation

Question 7

Maternal adaptation?

Answer 7

First pregnancies tend to be more prone to complications of mal-adaptation than subsequent gestations.

Pre-eclampsia is more common in first pregnancies as well as paternities (this risk is reduced if the couple have been having non-barrier sex for 12 months prior to conception)

Question 8

What is pre-ecplampsia?

Answer 8

Dangerously elevated maternal blood pressure accompanied by protein in the urine. Affects most maternal organs and is only found in pregnancy.

It is triggered by something in the placenta and is an exaggerated inflammatory response leading to vascular dysfunction. (failure of the normal maternal vascular adaptaion)

Question 9

Cardiovascular adaptations?

Answer 9

1. Increased cardiac output (10% increase in SV and 10-15% in HR)
2. Reduced peripheral vascular resistance

Pregnancies complicated by pre-eclampsia are characterised by higher than normal peripheral resistance.

Most of these changes occur prior to 9 weeks of gestation

Question 10

Causes of cardiovascular adaptations?

Answer 10

• not due to oestrogen as levels are low at this stage
• not progesterone as it doesn’t have systemic effect and levels are also low at this stage
• Angiotensin (vasoconstrictor) increases in pregnancy and the uteroplacental unit prosuces large amounts of the RAS but the effects appear to be blunted in normal pregnancy
• NO produced by vascular endothelial cells is also increased in pregnancy

Question 11

Haematological Changes?

Answer 11

1. Increased blood volume
2. Plasma volume and blood volume both increased in human pregnancy but at a different rate.
3. Thus, haematocrit declines in pregnancy as the plasma volume increases at a higher rate (about 1250mL by 30 weeks and then is stable)

NB: about 500mL is lost in delivery and 1L in Caesarean section so this begins the process of returing blood volume to a normal level.

Question 12

Haematological changes in menstrual cycle?

Answer 12

1. There are cyclic changes in blood/plasma volume during the menstrual cycle. At 8-10 weeks there is an estimated 10% increase in plasma volume that is similar to that seen in the menstrual cycle.

Thus, it is not this blood volume expansion that is causing the cardiovascular changes.

Question 13

Immune system adaptations?

Answer 13

The fetus is genetically half paternal and half maternal.

Yet, for 9 months the fetal tissue of the placenta and extraplacental membranes survive in intimate contact with the maternal immune system.

Some infections if first encountered in pregnancy may be more severe

Question 14

Immune cell changes?

Answer 14

• WBC count rises due to expansion of neutrophil population commencing in the leuteal phase with a peak at 30 weeks.
• Lymphocytes constant but with a tilt towards more (T helper CD4 cells) Th2 cytokines being produced driving antibody mediated response over Th1’s cell mediated response.

The decidua:

• Contains almost no B cells (no antibody production)
• 10% of immune cells are T cells with 70% of leucocytes being specialised uterine natural killer-like cells (lack receptors to act by AB-dependent cell mediated cytotoxicity)

This all limits the ability to kill the embryo in the uterus

Question 15

Abdominal wall and skin changes?

Answer 15

Blood flow to the skin increases

• warm clammy hands 6-7x increase
• Flow to feet also increases

Increased pigmentation of nipples and areola

Development of linea nigra (line down middle of abdomen)

Chloasma in the neck and face

All due to a increase in secretion of melanocyte stimulating hormone showing marked elevation in 2nd month of pregnancy. (suntans develop well in pregnancy)