57.2 Pregnancy Flashcards by Philip O'Mahony

Summarise the general structure of the placenta.

The placenta is essentially the interface between the maternal blood and the fetal blood:

Fetal vessels pass via the umbilical cord and form branches within villi
These villi are surrounded by intervillous spaces, which are supplied by the maternal blood
Thus, the fetal blood and maternal blood are completely separated, so the surface of the villi is required for exchange and immunological protection

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What are placental villi?

Placental (a.k.a. chorionic) villi are villi that sprout from the chorion to provide maximal contact area with maternal blood.

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Where on the uterus does the placenta usually form?

On the upper posterior aspect of the uterine wall.

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When does the development of the placenta begin? What happens here?

DAY 9 when lacunae (fluid filled holes) form within the syncitiotrophoblasts

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Describe the development of the placenta.

Begins with implantation, including attachment, penetration and decidual reaction
The syncytiotrophoblast cells are fused, then maternal blood fills the lacunae in the
The cytotrophoblastic cells begin to develop and the layer buldges out, forming primary villi -> These eventually develop into tertiary villi
Thus, the syncytiotrophoblast and crytotrophoblast form the outer lining of placental villi, which are surrounded by maternal blood

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What are the stages of placenta formation?

Formed from the trophoblasts
Primary chorionic villi
Secodnary chorionic villi
Teritary chorionic villi

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How do primary chorionic villi form?

Cytotrophoblast penetrates and expands in the surrounding syncitiotrophoblasts

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How do secondary chorionic villi form?

Embryonic pole trophoblasts lose their cell membranes and becomes the syncitiotrophoblasts
Trophoblasts lining blastocyst keep cell membranes and become cytotrophoblasts

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How do tertiary chorionic villi form?

Embryonic vessels begin to form in the poliferating embryonic mesoderm to form teritary chorionic villi
(end of third start of fourth week when placenta can now function)

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Describe the differences in the composition of the different stages of the chorionic villi

Primary = trophoblast only
Secondary = trophoblast and mesoderm
Teritary = trophoblast, mesoderm and blood vessels

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In summary, what tissue is the placenta derived from?

Trophoblast

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Which layer other than the trophoblasts and mesoderm also forms the mature placenta?

Decidua basalis (part of endometrium that takes part in placental formation)

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How is the intervillous space produced?

Lacunae filled with maternal blood fuses together to form large intervillous spaces which the synctiotrophoblasts protrude into

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What is the function of the placenta?

-Synthesis of hormones
-Transfer of respiratory gases (lungs), nutrients (GI tract) and waste products (liver)
-Physical attachment of conceptus to uterus
-Invasion and digestion of endometrial tissues

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What has been circles below?

Primary villi - cytotrophoblasts invading syncytiotrophoblasts

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What are the major peptide hormones secreted by the placenta?

hCG (human chorionic gonadotrophin)
hPL (human placental lactogen)- also known as human chorionic somatomammotrophins (hCS)
Relaxin - relaxes pelvic joints and ligaments and softens cervix for partuition

Which steroid hormones are important in pregnancy?

Oestrogens (Oestradiol, oestriol and oestrone)
Progesterone

Which oestrogen is not important in non pregnant women but vital for pregnancy?

Oestriol

What are the steroid hormones secreted by the placenta?

Steroid hormones:

Estrogens -> Esterone, Esteriol, Estradiol
Progesterone

What part of the placenta produces peptide and protein hormones?

Syncytiotrophoblast cells

What is the importance of hCG and where is it produced?

Produced in the syncytiotrophoblast
It signals the presence of a fertilised egg, maintaining the corpus luteum and stimulating its production of progesterone
Progesterone is important in stopping the shedding of the endometrium and preventing contractions of the myometrium
This progesterone from the corpus luteum is important for the first 6-8 weeks of pregnancy, until the placenta is established and becomes the main source of progesterone

(Thus, hCG levels drop around 10 weeks, but continue to be produced)

What is the importance of hPL and where is it produced?

Produced in the syncytiotrophoblast of the placenta
It rises in concentration in the maternal circulation between 8 and 35 weeks
Has weak GH and PRL activity -> Therefore, increases somatic growth in the mother (e.g. breast growth) and increases milk secretion
Also has metabolic effects -> Increases nutrient concentrations in the blood, for better supply to the fetus (e.g. increases maternal lipid breakdown)

What does hPL stand for?

Human placental lactogen

What changes in maternal metabolism does hPL cause? Why?

Reduces insulin sensitivity to maternal tissues (diabetogenic effect) to increase plasma glucose levels
Increases use of FFA used by mother and decreased glucose use to preserve the fuel
Increased foetal insulin secretion to take up the glucose
Suppression of gluconeogenesis from amino acids - useful supply for fetus

Summarise the effects of hPL.

* hPL essentially has diabetogenic effects, increasing concentrations of sugar and fatty acids in the blood for the fetus. * This can lead to gestational diabetes

Describe the changes in concentration of the different steroids involved in pregnancy and where they are produced.

* At first, after implantation happens, hCG from the placenta (syncytiotrophoblast) maintains the corpus luteum -\> Thus, the ovaries produce most of the progesterone at first * By the second trimester, the corpus luteum has degraded and the placenta has developed -\> More progesterone and estrogen are produced from the placenta, as hCG decreases * In the third trimester, there is very little hCG, while progesterone and estrogen peak

Describe the concept of the maternal-placental-fetal unit.

* The mother requires progesterone and estrogens for maintaining pregnancy * The mother provides the LDL cholesterol required for synthesis of these, but she lacks the enzymes to produce them, so she cannot synthesise them along * Therefore, a maternal-placental-fetal unit is required for synthesis -\> The placenta and fetal adrenal/liver provide the enzymes for progesterone and estrogen synthesis (Details of enzymes are not core)

Why is the foetus needed in the maternal-placental-fetal unit?

Foetal liver contains the enzyme 16 alpha hydroxylase needed to make an intermediate to synthesise estriol Foetal adrenal gland contains enzymes needed to make DHEA -sulphate (weak androgen)

Summarise the functions of oestrogens during pregnancy.

-Growth of uterus -Increases pliability of connective tissues -Increases development of breast tissue (replace role of hPL) -Opposes natriuresis and diuresis (sodium and water retention) to increase blood volume -Vasodilation to prevent hypertenion (produces NO linked vasodilators)

Why is it important that the fetus cannot do complete biosynthesis of oestrogens and prosgesterones? How is this overcome?

It would expose dangerously high levels of hormones not needed by the fetus Fetus cannot make anything past DHEA and 16 alpha OH -DHEA which it then delivers to the placenta which acts as a large sink of weak androgens to prevent masculinisation of female fetuses Fetus sulphates intermediates to reduce their biological activity

What happens to levels of hCG during pregnancy?

Spikes during the first trimester then falls (no need to maintain corpus lutetum)

Summarise the functions of progesterone during pregnancy.

the placenta takes over from the corpus luteum as the major source of progesterone at week 10 to maintain the endometrium and reduce myometrial excitability (via down-regulation of oxytocin and oxytocin receptors) as well as to stimulate mammary development in readiness for lactation

What happens in amniocentesis?

50-100ml of amnionic fluid is aspirated and foetal cells are cultured and karyotyped to check for chromosomal abnormalities, single gene disorders and for alpha-fetoprotein (sign of spina bifida)

When is amniocentesis done compared to chorionic villus sampling?

Amniocentesis = 16-20 weeks Chorionic villus sampling = 11-14 weeks

What is chorionic villus sampling?

Suction tube used to remove foetal cells from the chorion (early placenta) to look for (a) chromosomal abnormalities; (b) single gene disorders; (c) transplacental virus infection (e.g. Rubella); and (d) foetal blood grouping (e.g. Rh).

What are the relative risks of miscarriage for amniocentesis and CVS?

Amniocentesis = 0.5-1% CVS = 2%

How may a foetus be examined morphologically?

Ultrasound or MRI

Explain the concept of foetal programming.

* The concept is that a person's health can be largely affected by the conditions they face when they are still a fetus * For example, risk of Type 2 diabetes and hypertension is affected by fetal conditions. * Those born underweight have a reduced life expectancy. This is in part due to long-term programming of the glucocorticoid stress axis, which becomes chronically overactive.

How does LH contribute to pregnancy?

The second half of the menstrual cycle (days 14–28), following ovulation, is the luteal phase. The post-ovulatory follicle becomes a corpus luteum under the influence of LH. The corpus luteum secretes progesterone which prepares the uterus to receive and nourish an early embryo in the event of fertilization