The Physiology of Pregnancy 1

Question 1

Why are there troubles in studying the placenta?

Answer 1

Hard to convince pregnant women to do invasive experiments, and instead we have to use other species.

The human placenta is major source of steroid hormones, whilst the corpus luteum continues to produce progesterone throughout pregnancy.

But the amount and variations of hormones we produce is far greater then any other specis, so its hard to comparre

Question 2

Placenta is a rich source of hormones and othercompounds, what is the significance of these?

Answer 2

The significance of many of these hormones is unclear (eg GnRH)

But Hormones such as placental growth hormone variant and hPL may have been important in the past during starvation.

Note that pregnancy involves both mum and baby to contribute to the endocrine balance, so you have 2 patients

It seems to produce everything

Question 3

Hormone 1: Human Chorionic Gonadotrophin (hCG)

WHat is it, where is it produced and when can you detect it?

Answer 3

• 2 Chain hormone that shares it’s a chain with TSH, LH and FSH​
  
  • The hormones all have a unique B chain
• BhCG is produced only by:
  
  • syncytiotrophoblast of the placenta
  • trophectoderm of the preimplantation blastocyst cells that will become the embryo
• BhCG is detectable in the maternal blood/urin within days of implanatation

Question 4

SImilarities/differences between hCG and LH?

Which one can be used as a diagnostic test?

Answer 4

Very similar hormones, that share an alpha chain and have very similar properties.
BUT LH has a much shorter half-life → for a quick spike leading to ovulation

BhCG has an extension via the Beta chain (33aa longer), which promotes the half life of BhCG in the blood → t_1/2 ~24hours

This makes hCG a good diagnostic test

Question 5

BhCG as a diagnostic tool?

Answer 5

Used to confirm pregnancy via detection of BhCG in urine dipsticks or blood samples.

BhCG secretion increased rapidly in the 1^st weeks of pregnancy and peaks at 100,000units/ml at 10 weeks gestation

Post 10 weeks: levels drop off to ~20,000units/ml

• First line: control line (shows testing unit is functional)*
• Second line: confirms pregnancy*

Question 6

What do they mean by hCG tests working upto 3 days of your period

Answer 6

Because 3 days before your expected period in a 28 day cycle is day25.

Implantation occurs ~ day 21
(takes 7days to implant post ovalutation at day 14).

Therefore can detect the pregnancy even before the first missed menstrualperiod

Question 7

What’s the Function of hCG during the first 6-8weeks of preganacy?

Answer 7

• Binds to the LH/hCG receptor (shared) and transmits a similar signal to LH
• Luteal Support
  
  • hCG has strong leutotrophic properties: important in stimulating progesterone and oestrogen production by the ovary in the first 6-8weeks of pregnancy
  • Stops regression of the corpus luteum (tells mum she is pregnant)
• THe Corpus Luteum doubles in size about a month into pregnancy under the influence of hCG

Question 8

What’s the function of hCG after the first 6-8weeks of preganacy?

Answer 8

Around now the placenta takes over from the ovary as the major source of progesterone.

• Now hCG main function: stop the uterus from returning to its normal cyclic pattern.
  
  • Does this by stimulating Corpus Luteum to continue secreting progesterone/eostrogen
  • These prevent menstruation and maintain the endometrium in a decidualised form
• Women with ovarian cancer can have oophorectomy past this point and maintain pregnancy as ovaries are no longer needed

Question 9

Why is there more hCG present withmultiple pregnancies (eg twins)?

Answer 9

hCG is produced by the syncytiotrophoblast of the placenta, therefore hCG produced in proportional to placentalmass.

In twins there is an increased amount of syncytiotrophoblast present → more hCG.

Question 10

How has the importance of hCG in maintaining pregnancy been proven?

Answer 10

Via a vaccine which target hCG, and is used as a contraceptive method. (got to phase 2 clinical trials)

High levels of BhCG antibodies following vaccination → induced infertility

Question 11

What type of tumours produce high levels of hCG?

Answer 11

Trophoblastic tumours.

• Choriocarcinoma (cancer of uterus) and hydatidiform mole (are mass or growth that forms inside the womb (uterus) at the beginning of a pregnancy​)
• also some testicular tumours

Question 12

Why is hCG so important in pregnancies of male fetuses?

Answer 12

As it is so similar to LH, it produces LH-like activity.

It stimulates synthesis by leydig cells of the fetus testis → stimulates testosterone → drives sexual differentiation

At this early point in development, the pituitary (and therefore LH) have nott formed so you need a replacement.

THis is crtitical for phenotypic sexual differation of males?

Question 13

How is it that women with high hCG levels can get hyperthyroidism?

Answer 13

A consequence of the 4 hormones LH, FSH, TSH and hCG being so structurally similar is that there is cross reactivity.

SO hCG can lead to stimulation ofthe TSH receptor (or via the LH receptor) in the thyroid.

So choriocarcinoma and hydatidiform moles which produce hCG at very high levels can become hypethyroid

Question 14

Hormone 2: Progesterone

What is it synthesised from?

Answer 14

Synthesised by the

Syncytiotrophoblast of Placenta: shown by choriocarcinoma and hydatidiform moles produce progesterone by themselves

But as trophoblasts can’t convert Acetate → Cholesterols, it instead uses LDL-cholesterol derived from maternal circulation.

The Syncytiotrophpblasts expresses various receptors to assist this LDL uptake.

Question 15

How does the LDL receptor level on syncytiotrophoblast change throughout pregnancy?

Answer 15

Early on:
Loosely held within the tissue

Mid-gestation/term:
Densely packed into the syncytiotrophoblast very strongly. (to pick up lots of LDL for building higher levels of progesterone as gestation progresses)

Question 16

Is the fetus required for progesterone production by the placenta, and why?

Answer 16

No because

1. Ligation of the cord doesn’t cause an immediate drop in circulating progesterone levels
2. Removal of the ovaries (with it’s CL) doesn’t compromise human pregnancy after 6 weeks gestation
   
   • Suggests placenta is now producing adequate progetsterone to maintain the pregnancy

Question 17

What are the functions of Progesterone during pregnancy?

Answer 17

• Maintains uterine quiescence
• Converts (along with oestrogens which primes expression of the P₄ receptors) the uterine environment → environment conductive of pregnancy
  
  • P₄ receptors are expressed by both glands and stromal cells in the endometrium/decidua
  • Induces formation of the Decidua

Question 18

What is the decidua for?

Why is it not essential for implantation

Answer 18

Specialised tissue required for supply nutrient (decidual reaction) prior to ‘tapping’ the maternal blood supply.

Not essentialfor pregnancy as proved by anyectopic pregnancy.

But it may be important for regulating the extent of implantation. if so it’s important to maintain during pregnancy

Question 19

Hormone 3: Oestrogens

What are they produced by and what is required for this, how do the levels change through preganancy

Answer 19

• Produced in large quantities by the feto-placental unit, requires
  
  1. A live fetus (unlike P₄)
  2. Function Fetal Adrenals
  3. Intact Feto-placental circulation
  4. A functioning placenta
• There’s a 1000-fold increase in oestorgens in pregnancy.
  *

Question 20

Why does there need to be collaberation between the fetus and the placenta in order to produce oestrogens?

Answer 20

• Placenta can’t produce 17a hydrolyase enzyme so can’t (progesterone → Androgens)
  
  • hydratidiform moles and choriocarcinomas can’t produced oestrogen, only progesterone
• ​​Placenta can aromatise Testosterone/androstenedione/dehydroepiandrostene → estrogen/oestrodial
• Fetal adrenals can P₄ → Androgens (androstenedione + dehydroepiandrostene) but can’t convert them to oestrogens
• So progesterone gets shunted to adrenalsand liver (requires live fetal circulation) and then back to placenta to be aromatised

**this is why Anencephalic pregnancies (atrophic adrenals) there’s low levels of oestrogens

​

Question 21

Where does oestrogen/progesterone go once produced?

Answer 21

Oestrogen: more the >90% of placental E₂ enter the maternal circulation

Progesterone: more then >85% of placental P₄ enter the maternal circulation.

This is because they are mostly produced in the syncytiotrophoblast, which are these single multi-nucleiated cell layer covering the entire placental surface; directly in contact with maternal blood, whereas the fetal circulation is several cell layers down

• through villous trophoblast, stromal tissue of placenta, BM, capilliary endothelum → fetus

Question 22

Maternal Adaptions occur in what systems.

WHy do they occur?

Answer 22

• The maternal Cardiovascular system
• The Haematological system (blood itself)
• The maternal Immune System
• The Genital System

Profound changes take place in the maternal physiology to allow gestation to proceed for 9 months.

1^st more prone to mal-adaptation, so mother cannot change effectively (higher rates of preeclampsia in 1^st pregnancies.

If you’ve had a baby you’re protected against many diseases

Question 23

What is Preeclampsia?

Answer 23

Elevated maternal BP after 20 weeks gestation. Often accompanied by proteinuria.

Caused from multi-organ dysfunction (brain > visual disturbia, impaired liver function, renal insufficiency, pulmonary thrombocytopenia)

• Affects most maternal organs
• Triggered from something from the placenta (only occurs in pregnant women)
• An exaggerated inflammatory response → vascular dysfunction
• Falure of the normal vascular adaptation to pregnancy
• Loss of the normal maternal peripheral vascular resistance relaxation: see Hypertension weeks before clinical diagnosis

Question 24

What are the Cardiovascular Maternal Adaptations during pregnancy?

Answer 24

• Increased Cardiac Output: Caused by
  
  • 10% increase in SV
  • 10-15% increase in pulse rate
  • In normal person this would increase BP, which is compensated for by…..
• Reduced Peripheral Vascular resistance

Preeclamptic pregnancies are characterised by higher then ‘normal’ peripheral resistance

Question 25

How quickly do these cardiovascular adaptations occur?

Answer 25

The change in Cardiac output is rapid early in pregnancy.

5wks post LMP (2wks post implantation): exponential increase in CO initial