Disorders of Early Development Flashcards
3 causes of pregnancy loss in humans
Errors in embryo-fetal development
Failure of embryo to implant in the uterine lining
Inability to sustain the development of an implanted embryo/fetus
Define miscarriage
loss of pregnancy PRIOR to 23 weeks of gestation
What occurs around 23/24 week mark?
Fetus acquires viability (can survive outside the womb)
Distinguish between early and late clinical pregnancy loss
Early <12 weeks gestation
Late <24 weeks gestation
What is RM/RPL?
Recurrent miscarriage/recurrent pregnancy loss
How is RM/RPL defined in UK vs USA?
UK: 3+ losses
USA: 2+ losses
Can be consecutive/non-consecutive
What are pre-clinical pregnancy losses & give details on proportion of losses?
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
What is the proportion of clinical pregnancy losses?
15% - e.g. miscarriage
Major cause of early pregnancy loss?
Chromosomal abnormalities - aneuploidy
Effect of age on trisomy?
As maternal age increases, risk of trisomy increases
35+ risk increases exponentially
How is genetic information exchanged between homologues?
Recombination
What occurs during meiotic arrest & how long can it last for?
A break in meiosis of the oocytes which resumes before ovulation
Can last up to 50yrs
How are homologous proteins held during meiotic arrest?
COHESIN proteins
What happens to cohesin proteins over time & what’s the effect of this on chromosomes?
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
2 examples of cohesin proteins that are lost with age
SMC2
REC8
Explain the products of maternally and paternally imprinted genes
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.
What are gestational trophoblastic diseases?
Disorders characterised by overgrowth of trophoblastic tissues
Examples of malignant and benign GTDs
Malignant - gestational trophoblast neoplasms
Benign - partial/complete hydatidiform moles
Distinguish between partial and complete hydatidiform moles
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🧏🏾♀️
Which gene contributes to recurrent hyatidiform moles?
NLRP7 (remember ‘not like regular preganancy 7’)
NLRP7 gene is mutated and the endoderm fails to recognise molar pregnancies
Describe the appearance of a molar pregnancy placenta
There are grape like villi
What is an ectopic pregnancy
An extra-uterine implantation
Commonly in the fallopian tubes (FT) - 98%
Treatments and cautions of ectopic pregnancy
Surgery to remove trophoblast/tube
Chemotherapy
Risk of rupture - can lead to internal bleeding
What molecules in cigarettes contribute to ectopic pregnancy & how?
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
Factors that increase risk of ectopic pregnancy
Prior ectopic pregnancy Prior FT surgery Endometriosis STIs Pelvic inflammatory disease Smoking cigarettes Aged 35+ Infertile history IVF use ☹️
