Disorders of Early Foetal Development Flashcards
What are the 3 causes of pregnancy loss?
Errors in embryo-foetal development
Failure of the embryo to implant in the uterine lining
Inability to sustain development of an implanted embryo/ foetus
What is a recurrent miscarriage?
UK: 3 or more pregnancy losses (consecutive/ non-consecutive)
USA/ Europe: 2 or more pregnancy losses (consecutive/ non-consecutive)
How frequent is pregnancy loss?
preclinical pregnancy loss
- 30% conceptions lost prior to implantation
-30% following implantation but before the menstrual period
clinical pregnancy losses
- 15% of conceptions
10% 20-24 y/o
51% in 40-44 y/o
What is the major cause of early clinical pregnancy loss?
Aneuploidy (chromosome number errors) in embryo
Exponential increase in the risk of trisomic pregnancy with increasing maternal age
Why increasing maternal age increases risk of miscarriage (pathophysiological detail)?
Loss of cohesion between homologous chromosomes in oocyte, due to cohesins degrading as you get older (and are not replaced)
If cohesion has been lost, chromatids can separate and drift during meiotic division, rather than being segregated accurately by the spindle
Name 2 examples of cohesion proteins.
REC8 and SMC2
Oocyte experience prolonged meiotic arrest, explain this?
The waiting at a particular stage of meiosis by the oocyte until some stimulus is received, usually the entry of the sperm
- the prophase of the first meiotic division
When is meiosis resumed after the meiotic arrest?
just before ovulation
Embryos require maternal and paternally derived genomes to be viable, i) state a two-word phrase which explains the cause of this, ii) using one word, describe which type of embryo arises when we have 2 sets of the maternal genome fertilising an egg, iii) using one word, describe which type of embryo arises when we have 2 sets of the paternal genome fertilising an egg
i) Genomic imprinting
ii) Maternal genome x2 = parthenogenetic embryo (small placenta)
iii) Paternal genome x2= androgenetic embryo (big placenta)
What are gestational trophoblastic diseases?
a collection of disorders characterised by overgrowth of trophoblastic tissue
What two broad types of gestational trophoblastic diseases are there?
benign or malignant
What are example(s) of benign gestational trophoblastic diseases?
Hydatidiform mole- overgrowth of trophoblastic cells
NLRP7 mutations may underlie recurrent hydatidiform mole
2 types of hydatidiform moles:
- Complete hydatidiform mole (empty egg fertilised by 1x sperm then sperm genome duplicated
or 2x sperm (no duplication)); foetal tissue absent - Partial hydatidiform mole (normal egg fertilised by 1x sperm then sperm genome duplicated
or 2x sperm (no duplication)); foetal tissue present
What are example(s) of malignant gestational trophoblastic diseases?
rare:
invasive mole
choriocarcinoma
very rare:
placental site trophoblastic tumour (PSTT)
epithelioid trophoblastic tumour
What is an ectopic pregnancy?
Implantation of the embryo at a site other than the uterine endometrium (usually in the fallopian tube)
1-1.5% of pregnancies are ectopic
How are ectopic pregnancies treated?
chemotherapy (methotrexate)
surgery to remove the affected tube
What can the rupture of fallopian tubes lead to?
Severe internal bleeding and high risk of death
Describe 2 adaptations of the fallopian tubes.
Smooth muscle contraction which facilitates the movement of the embryo along the uterine tube
Epithelium coated in cilia to promote fluid movement
What are some risk factors fro ectopic pregnancies?
maternal cigarette smoking
cannabis use
prior ectopic pregnancy
prior fallopian tube surgery
certain STIs: chlamydia and gonnoreahea
pelvic inflammatory disease (PID)
endometriosis
history of infertility
use of assisted reproductive technology, such as IVF
age (older than 35)
Why is maternal cigarette smoking a risk factor for ectopic pregnancies?
Cotinine- component of cigarette smoke, regulates the expression of PROKR1, a regulator of fallopian tube smooth muscle contractility; may inhibit action of smooth muscle= failure to transit
Increase expression of pro-apoptotic proteins in fallopian tube explants, cilia can block the tube -BAD gene
Tobacco smoke likely to inhibit ciliary function- reducing transit of the embryo
Why is cannabis a risk factor for ectopic pregnancy?
Fallopian tube expresses CB1 and CB2 cannabinoid receptors
CB1 reduced in ectopic pregnancy patients, and CB1 knock-out mice causes embryo retention in the fallopian tubes
Levels of endocannabinoids elevated in ectopic pregnancy fallopian tubes
THC in cannabis may act directly on the fallopian tubes to disturb transit or alter the balance of endocannabinoids in the tube leading to disrupted embryo environment
