Lecture 13: The Placenta and pregnancy (III)

Question 1

Describe the structure of Human Chorionic Gonadotrophins

Describe what produces the hCG

Answer 1

• Two chain hormone that shares it’s αchain with TSH, LH and FSH
• The hormones all have a unique βchain
• βhCGis produced exclusively by the syncytiotrophoblast of the p_reimplantation blastocyst_ and placenta
• βhCGis detectable in the maternal blood/urine within days of implantation

Question 2

βhCGis produced exclusively by the ________of the _______and ______

Answer 2

βhCGis produced exclusively by the syncytiotrophoblast of the preimplantation blastocyst and placenta

Question 3

We can use hCG clinically as an indicator of….

Answer 3

Indicator of health of the pregnancy

Question 4

What are the functions of hCG?

Answer 4

• •hCG binds to the LH/hCG receptor and thus transmits similar signals to LH. (the half life is longer than LH)
• •Luteal support:
  
  • •hCG has strong leutotrophic properties and is important in _stimulating the production of progesterone and oestroge_n by the ovary during the first 6-8 weeks of pregnancy.
  • •stops regression of the corpus luteum.
• •The CL doubles in size about a month into pregnancy under the influence of hCG
  
  • •After this time point the placenta takes over from the ovary as the major source of progesterone.
• •hCG is basically responsible for preventing the uterus returning to its normal cyclic pattern by causing the CL to continue to secrete Prog and oestrogen.
• •These hormones prevent menstruation and maintain the endometrium in a decidualised form.

Question 5

hCG binds to the _______receptor and thus _______

Answer 5

hCG binds to the LH/hCG receptor and thus transmits similar signals to LH.

Question 6

Women with multiple pregnancies have _______ levels of HcG

Answer 6

Women with multiple pregnancies have increased levels of hcG

This is because of the increased amount of syncytiotrophoblast in twin pregnancy

Question 7

The importance of hCG in maintaining pregnancy can be seen int eh use of this hormone as a target for _______

Answer 7

Contraceptive vaccines

Question 8

Aside from pregnancy, high levels of hCG are found in _______

Answer 8

Trophoblastic tumours. Choriocarcinoma and hydatidiform mole, and also in testicular cancers

Question 9

Progesterone is synthesised by ………

Answer 9

Synctiotrophoblast of the placenta.

Shown by production by moles and choriocarcinomas

Question 10

Removal of the ovaries does not compromise human pregnancy after ________

Answer 10

6-8 weeks of gestation (may be required due to a tumour)

Question 11

Syntytiotrophoblast expresses various receptors to __________

Answer 11

Assist LDL uptake (when we make steroids, we make them from inorganic acetate, but trophoblasts cannot synthesise progesterone from acetate).

Because progesterone is crucial to pregnancy, the placenta is laden with receptors that carry LDL cholesterol from mum’s blood into the placenta.

Question 12

When we make steroids, we make them from inorganic acetate, but trophoblasts cannot synthesise progesterone from acetate. Therefore …….

Answer 12

Therefore instead, Syntytiotrophoblast expresses various receptors to Assist LDL uptake

Because progesterone is crucial to pregnancy, the placenta is laden with receptors that carry LDL cholesterol from mum’s blood into the placenta.

Question 13

What is the function of progesterone?

Answer 13

Progesterone maintains uterine quiescence (state of inactivity)

Along with oestrogens, progesterone converts the uterine environment to one that is conducive to pregnancy

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

Prog induces formation of the decidua. Decidua may just be specialised tissue that is important for providing nutrients prior to tapping the maternal blood supply but

The decidua is not essential for implantation as is demonstrated by ectopic pregnancy

It is postulated that decidua may be important for regulating the extent of implantation. If this is correct it is important to maintain the decidua throughout pregnancy

Question 14

Progestrone receptors are expressed by ________

Answer 14

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

Question 15

Prog induces formation of the _______.

Answer 15

Decidua. Decidua may just be specialised tissue that is important for providing nutrients prior to tapping the maternal blood supply but

The decidua is not essential for implantation as is demonstrated by ectopic pregnancy

It is postulated that decidua may be important for regulating the extent of implantation. If this is correct it is important to maintain the decidua throughout pregnancy

Question 16

The decidua is/is not essential for implantation as is demonstrated by _______.

Decidua may be important for…..

Answer 16

The decidua is not essential for implantation as is demonstrated by ectopic pregnancy

It is postulated that decidua may be important for regulating the extent of implantation. If this is correct it is important to maintain the decidua throughout pregnancy

Question 17

Can human placenta produce oestrogen de novo (“new”?

Answer 17

No, human placenta has no 17 alpha hydroxylase (convert progesterones to androgens)and cannot produce oestrogen de novo.

But placenta can aromatise testosterone, androstenedione and dehydroepiandrostene to oestrone and oestradiol

Question 18

If the fetus cannot produce oestrogen de novo, what does it do to?

Answer 18

human placenta has _no 17 alpha hydroxylas_e (convert progesterones to androgens)and cannot produce oestrogen de novo.

Fetal adrenals can produce androstenedione and dehydroepiandrostene but can not convert them to oestrogens.

But placenta can then a_romatise testosterone_, androstenedione and dehydroepiandrostene to oestrone and oestradiol

Anencephalic pregnancies (in which the adrenals are usually atrophic) usually have low levels of oestrogens

Question 19

What are the maternal adaptations during pregnancy

Answer 19

Changes occur in

•Most systems of the body including
•The maternal cardiovascular system
•The haematological system
•The maternal immune system
•The genital system

Question 20

_____% of progesterone and estrogen produced in the placenta are shuffled into the maternal blood not the fetal blood

Answer 20

85-90%

Question 21

Preecalmpsia is more common in ______

Answer 21

First pregnancies/paternities

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

Question 22

What is Preeclampsia?

Answer 22

Preeclampsia –dangerously elevated maternal blood pressure accompanied by protein in the urine

• Affects most maternal organs
• Found only in pregnancy
• Triggered by something from the placenta
• An exaggerated inflammatory response leading to vascular dysfunction
• Failure of the normal vascular adaptation to pregnancy.
• loss of the normal m_aternal peripheral vascular resistance_ (normally resistance relaxes)

Question 23

Describe the Cardiovascular adaptations in normal pregnancy vs during preeclampsia

Answer 23

Most important changes are

• Increased cardiac output
• Caused by a 10% increase in stroke volume and 10-15% increase in pulse rate.
• Reduced peripheral vascular resistance

Pregnancies complicated by preeclampsia are characterised by higher than “normal” peripheral resistance.

Question 24

Describe the role of Oestrogen on CV changes

Answer 24

• Can reduce vascular resistance mainly in reproductive tissues
• Can alter the ratio of type I /type III collagen in the vessel wall
• High levels of oestrogen a_re not reached until 9 weeks_ when fetal adrenals induce synthesis.

Question 25

Describe the role of Progesterone on CV changes

Question 26

Describe Angiotension II and CV changes

Answer 26

* Angiotensin II (AII) is basically a vasoconstrictor which causes the arterioles to contract and thereby increases BP –its levels increase in pregnancy * The uteroplacentalunit produces large amounts of the RAS * The effects of AII appear to be blunted in normal pregnancy * possibly due to receptor changes

Question 27

Describe the role of NO and CV changes

Answer 27

* NO is produced by vascular endothelial cells by nitric oxide synthetase in response to the shear stress of blood flowing over the vessel surface. * Nitric oxide has a ½ life of 6 seconds and causes arterial wall relaxation and dilation. * The activity of nitric oxide synthetasein some tissues is increased in pregnancy.

Question 28

Describe the Haematolgical changes with pregnancy (changes in blood)

Answer 28

1) Increased blood volume 2) _Plasma volume and blood volume_ both _increase_ in human pregnancy but at different rates. 3) Thus the _haematocrit (blood cell volcume) decline_s in pregnancy as plasma volume increases at a higher rate than cell mass 4) Plasma volume increases by 1250 mls by 30 weeks and thereafter remains stable.

Question 29

When you're checking a blood test of a pregnant woman....always........

Answer 29

Check the values against the "normal" values of a pregnant woman Plasma volume and blood volume both increase in human pregnancy but at different rates.

Question 30

During delivery there is __________ (Haemotological Changes)

Answer 30

During delivery there is substantial blood loss 500mls for a singleton vaginal delivery 1 litre for twins and about 1 litre during caesarean section. Thus, the heamatocritslowly returns to normal postpartum.

Question 31

What drives the CV changes in normal pregnancy?

Answer 31

Lots of possibilities but we are not certain But if this doesn't occur properly, can result in preeclampsia

Question 32

Describe the Immune responses to pregnancy

Answer 32

* There is some evidence for a _**diminution** of the maternal immune response_ to some organisms in pregnancy. * Some infections if first encountered in pregnancy may be more severe e.g. leprocy, colds * _White cell count rises_ due to expansion of the **neutrophil** population, which commences in the leutealphase of the cycle and does not drop with pregnancy. * Neutrophil counts peak at 30 weeks then rise again at the time of labour * Neurtrophil does not result in transplant rejection * **Lymphocyte** counts do not alter greatly in pregnancy but there is believe to be a bias in the type of T helper (CD4) cells and the cytokines they produce with a _tilt in the balance toward Th2 cytokines_ * **Th1** cytokines drive the immune system towards a c_ell mediated_ (cytotoxicT cell, ietransplant rejection) response * **Th2** cytokines drive the immune system towards an a_ntibody mediated_ response.

Question 33

\_\_\_\_\_\_\_ appears to be beneficial protecting against pre-eclampsia.

Answer 33

Repeated exposure to sperm appears to be beneficial protecting against pre-eclampsia. (with the sperm donor. New partner- reset risk)

Question 34

Describe the white cells in the decidua

Answer 34

•The decidua contains: * almost _no B cells_ (no antibody production) * about 1_0% of the leuocytes_ in the decidua are _T cells_ * _70% o_f the leucocytes are specialised uterine _natural killer-like cells. (incapable of killing via antibodies)_

Question 35

Majority of the leucocytes in the decidua are \_\_\_\_\_\_\_\_\_\_

Answer 35

70% of the leucocytes are _specialised uterine natural killer-like cells_. (incapable of killing via antibodies)

Question 36

What are recurrent miscarriages?

Answer 36

Three or more consecutive pregnancy losses. With each miscarriage, the chances of furture pregnancy decreases

Question 37

Compare mean CD3 T cell density in the placental bed of Recurrent Miscarraige vs normal pregnancy

Answer 37

Recurrent Miscarraige: higher decidual T cell

Question 38

Describe changes in skin during pregnancy

Answer 38

* _Blood flow to the skin is increased in pregnancy_ (reduce temp) * Pregnant women often have warm and clammy hands * Flow to the hands is increased 6-7 fold * Flow to the feet is also increased * These areas generally indicate raised flow to other skin regions. * There are _pigmentation changes in some area of skin nipple_s and areola * There is also development of a lineanigra * Chloasmamay develop mainly in the neck and face -lost or regress after pregnancy (usually) * These pigmentation changes are due to an increased secretion of melanocyte stimulating hormone which is markedly elevated from the second month of pregnancy. * Suntans develop well in pregnancy

Question 39

In the latter part of pregnancy approximately 50% of pregnant women develop \_\_\_\_\_\_

Answer 39

n the latter part of pregnancy approximately 50% of pregnant women develop **Striae Gravidarum-**reddish slightly depressed streaks –in the skin of the abdomen, thighs and breasts.