Implantation, the placenta and hormonal changes in pregnancy (repro)

Question 1

What is needed for implantation to occur?

Answer 1

A fully developed blastocyst:

• contains trophoblast, blastocoel and embryoblast or inner cell mass (ICM)
• fully expanded
• hatched out from zone pellucida

A receptive endometrium:

• thickened endometrial lining
• expression of embryo receptivity markers

Question 2

Implantation timeline (days 7-12)

Answer 2

Implantation has 3 stages:

• Apposition
• Attachment
• Invasion

Days 7-8:

• blastocyst attaches itself to surface of endometrial wall (decidua basalis)
• trophoblast cells start to assemble to from a Syncytiotrophoblast in order to facilitate invasion of the decidua basalis

Days 9-11:
- Syncytiotrophoblast further invades the decidua basalis and by day 11 its almost completely buried in the decidua

Day 12:

• decidual reaction occurs: high levels of progesterone result in enlargement and coating of decidual cells in glycogen and lipid rich fluid
• this fluid is taken up by the Syncytiotrophoblast and helps to sustain the blastocyst early on before the placenta is formed

Question 3

Implantation timeline (day 14)

Answer 3

Around day 14:

• cells of the Synctiotrophoblast start to protrude out to form tree-like structures known as Primary Villi, which are then formed all around blastocyst
• decidual cells between primary villi begin to clear out, leaving behind spaces known as Lacunae
• maternal arteries and veins start to grow into the decidua basalis
• these blood vessels merge with the lacunae - arteries filling lacunae with oxygenated blood and veins returning deoxygenated blood into maternal circulation
• blood-filled lacunae merge into a single large pool of blood connected to multiple arteries and veins
• known as Junctional Zone

Question 4

Placenta

Answer 4

• around day 17, foetal mesoderm cells start to form blood vessels within the villi, a basic network of arteries, veins and capillaries
• capillaries connect with blood vessels in umbilical cord (formed around week %)
• villi grows larger in size, develops into Chronic Frondosum
• at this point, endothelial cell wall and Synctiotrophoblast (villi) lining separate maternal and foetal red blood cells
• numerous maternal spiral arteries supply blood to each cotyledon, facilitating the maternal-foetal exchange
• in the 4-5th months of pregnancy, decidual septa form as they divide the placenta into 15-20 regions known as Cotyledons

Question 5

Placenta: maternal to foetal exchange

Answer 5

The foetus takes up:

• O2 and glucose
• immunoglobulins
• hormones
• toxins (in some cases)

The foetus drops off:

• CO2
• waste products

Question 6

Functions of placenta

Answer 6

• provision of maternal O2, CHO, fats, amino acids, vitamins, minerals and antibodies
• metabolism eg synthesis of glycogen
• barrier eg bacteria, viruses, drugs, etc
• removal of foetal waste products eg CO2, urea, NH4, and minerals
• endocrine secretion eg hCG, oestrogen, progesterone, hPL and cortisol

Question 7

Why is the placenta good at its job?

Answer 7

• huge material uterine blood supply (low pressure)
• huge surface area in contact with maternal blood
• huge reserve in function

Question 8

Disorders of placenta: Pre-eclampsia

Answer 8

• endothelial cell dysfunction leads to vasoconstriction and the kidneys retaining more salt causing hypertension
• causes reduced blood flow to kidney so glomerular damage and Proteinuria
• 3-4% of pregnancies
• > 20% weeks gestation (up to 6 weeks after delivery)
• results in placental insufficiency (inadequate maternal blood flow to the placenta during pregnancy)
• causes new onset maternal hypertension and proteinuria
• symptoms range from mild to life threatening
• primary cause is still unclear
• characterised by narrowing of the maternal spiral arteries supplying blood to placenta
• pre-eclampsia and seizures leads to eclampsia

Risk factors:

• first pregnancy
• multiple gestation
• maternal age >35 yrs
• hypertension
• diabetes
• obesity
• family history of pre-eclampsia

Question 9

Disorders of placenta: Placental abruption

Answer 9

• premature separation of all or part of the placenta
• symptoms include bleeding and pain in the back and abdomen
• caused by degeneration of maternal arteries supplying blood to placenta
• degenerated vessels rupture causing haemorrhage and separation of placenta

risk factors:

• blunt force trauma eg. car crash or fall
• smoking and recreational drug use (risk of vasoconstriction and increased blood pressure)
• multiple gestation
• maternal age >35 yrs
• previous placental abruption

Complications (maternal):
- hypovolemic shock
- Sheehan syndrome (perinatal pituitary necrosis)
- renal failure
- disseminated intravascular coagulation (from release of thromboplastin)
Complications (foetal):
- intrauterine hypoxia and asphyxia 
- premature birth

Question 10

Disorders of placenta: Placenta previa

Answer 10

• placenta implants in lower uterus, fully or partially covering the internal cervix
• associated with increased chances of pre term birth and foetal hypoxia
• cause still unclear
• endometrium in upper uterus not well vascularised

Risk factors:

• previous caesarean delivery
• previous uterine/ endometrial surgery
• uterine fibroid
• previous placenta previa
• smoking and recreational drug use
• multiple gestation
• maternal age >35 yrs

Question 11

Hormonal production during pregnancy

Answer 11

• foetal placenta formed from trophoblast cells
• produces human chronic gonadotrophin (hCG)
• low ratio of oestrogen: progesterone
  necessary for maintaining pregnancy

Question 12

Hormone levels during pregnancy

Answer 12

Oestrogen:
- gradually increases throughout pregnancy
- lowest level out of all the hormones
Progesterone:
- gradually increases throughout pregnancy then increase slows before end of pregnancy
- at a higher level than oestrogen
hCG:
- increases rapidly at the start of pregnancy then starts to rapidly decrease at the end of the 1st trimester
- slow decrease for the rest of pregnancy
- almost zero at end of pregnancy
hPL:
- rapidly increases at end of 1st trimester
- increase slows down at 13 weeks and becomes gradual
- level is higher than oestrogen but lower than progesterone

Question 13

Hormones to mother and foetus

Answer 13

• Cholesterol and LDL from mother to placenta then to foetus
• Cholesterol and LDL produces pregnenolone in placenta, mother and foetus
• Pregnenolone in mother makes DHEA-S
• Pregnenolone in placenta makes progesterone which is given to mother
• Pregnenolone makes DHEA-S in mother and foetus which makes DHEA in the placenta
• DHEA-S in foetus makes 16alpha-OH DHEA-S which is given to placenta
• 16alpha-OH in placenta makes 16alpha-OH androstenedione and estriol, then estriol is given to mother
• DHEA in placenta makes androstenedione which makes estrone which is given to mother
• Androstenedione also makes testosterone which makes estradiol which is given to mother
• hPL in placenta is given to mother

Question 14

Hormonal changes to the body pregnancy

Answer 14

• increased blood volume
• shallow breathing
• increased urinary output
• rise in oestrogen and progesterone
• mood changes
• nausea and taste changes
• loosened ligaments
• breast changes and darkened skin on areola

Question 15

Glossary

Answer 15

• Blastocyst: An embryo at a stage of development characterised by cells forming an outer trophoblast (trophectoderm) layer, an embryoblast (inner cell mass) and a blastocoel (fluid-filled cavity). The trophoblast layer gives rise to the placenta while the embryoblast layer gives rise to the foetus.
• Endometrium: The outer mucous membrane lining the uterus, which thickens during the menstrual cycle in preparation for possible implantation of a blastocyst.
• Decidua: Modified endometrium that is formed in response to progesterone, in preparation for pregnancy. Modification process is known as decidualisation.
• Placenta – A large organ that is formed during pregnancy, connecting maternal and foetal blood circulation. The placenta facilitates maternal-foetal exchange which is crucial for sustaining foetal development.
• Human Chorionic Gonadotrophin (hCG): A hormone produced by the placenta after implantation and an indicator of a successful pregnancy. Urine pregnancy tests are based on hCG detection.