Disorders of Early Development

Question 1

3 causes of pregnancy loss in humans

Answer 1

Errors in embryo-fetal development
Failure of embryo to implant in the uterine lining
Inability to sustain the development of an implanted embryo/fetus

Question 2

Define miscarriage

Answer 2

loss of pregnancy PRIOR to 23 weeks of gestation

Question 3

What occurs around 23/24 week mark?

Answer 3

Fetus acquires viability (can survive outside the womb)

Question 4

Distinguish between early and late clinical pregnancy loss

Answer 4

Early <12 weeks gestation

Late <24 weeks gestation

Question 5

What is RM/RPL?

Answer 5

Recurrent miscarriage/recurrent pregnancy loss

Question 6

How is RM/RPL defined in UK vs USA?

Answer 6

UK: 3+ losses
USA: 2+ losses
Can be consecutive/non-consecutive

Question 7

What are pre-clinical pregnancy losses & give details on proportion of losses?

Answer 7

They are pregnancy losses that occur before the pregancy is detectable

30% are lost pre-implantation
30% are lost post-implantation BUT BEFORE the missed menstrual period

Question 8

What is the proportion of clinical pregnancy losses?

Answer 8

15% - e.g. miscarriage

Question 9

Major cause of early pregnancy loss?

Answer 9

Chromosomal abnormalities - aneuploidy

Question 10

Effect of age on trisomy?

Answer 10

As maternal age increases, risk of trisomy increases

35+ risk increases exponentially

Question 11

How is genetic information exchanged between homologues?

Answer 11

Recombination

Question 12

What occurs during meiotic arrest & how long can it last for?

Answer 12

A break in meiosis of the oocytes which resumes before ovulation
Can last up to 50yrs

Question 13

How are homologous proteins held during meiotic arrest?

Answer 13

COHESIN proteins

Question 14

What happens to cohesin proteins over time & what’s the effect of this on chromosomes?

Answer 14

Cohesin proteins are lost over time & there is loss of cohesion between chromatids as the oocyte ages
Chromatids can thus, separate and drift during division & are not accurately segregated

Question 15

2 examples of cohesin proteins that are lost with age

Answer 15

SMC2

REC8

Question 16

Explain the products of maternally and paternally imprinted genes

Answer 16

MATERNAL - restricts embryo fitness to conserve resources for future pregnancies. Results in small placenta, large baby

PATERNAL - promotes embryo fitness at the mums expense. Results in massive placenta, small baby.

Question 17

What are gestational trophoblastic diseases?

Answer 17

Disorders characterised by overgrowth of trophoblastic tissues

Question 18

Examples of malignant and benign GTDs

Answer 18

Malignant - gestational trophoblast neoplasms

Benign - partial/complete hydatidiform moles

Question 19

Distinguish between partial and complete hydatidiform moles

Answer 19

Complete - empty egg is fertilised by 1 sperm (genome duplicated) OR two sperm (no duplication)
Partial - normally fertilised egg fertilised by 1 sperm (genome duplicated) OR 2 sperm (no duplication)

This drives placenta growth🧏🏾‍♀️

Question 20

Which gene contributes to recurrent hyatidiform moles?

Answer 20

NLRP7 (remember ‘not like regular preganancy 7’)

NLRP7 gene is mutated and the endoderm fails to recognise molar pregnancies

Question 21

Describe the appearance of a molar pregnancy placenta

Answer 21

There are grape like villi

Question 22

What is an ectopic pregnancy

Answer 22

An extra-uterine implantation

Commonly in the fallopian tubes (FT) - 98%

Question 23

Treatments and cautions of ectopic pregnancy

Answer 23

Surgery to remove trophoblast/tube
Chemotherapy

Risk of rupture - can lead to internal bleeding

Question 24

What molecules in cigarettes contribute to ectopic pregnancy & how?

Answer 24

CONTININE
disrupts the signalling of PROK with PROKR1, reducing smooth muscle contraction of FT thus the embryo cannot move along
induces pro-apoptosis protein expression in the FT
TOBACCO
inhibits cilia function and reduces the movement of the embryo through the FT

Question 25

Factors that increase risk of ectopic pregnancy

Answer 25

Prior ectopic pregnancy
Prior FT surgery
Endometriosis
STIs
Pelvic inflammatory disease
Smoking cigarettes
Aged 35+
Infertile history
IVF use ☹️