2: Disorders of early development Flashcards
Pregnancy loss can arise from
- errors in embryo-fetal development (e.g aneuploidy)
-failure of the embryo to implant in uterine lining
-inability to sustain development of an implanted embryo/fetus
Miscarriage is
loss of pregnancy prior to 23 weeks gestation
early clinical pregnancy loss (<12 weeks gestation)
Late clinical pregnancy loss (>24 weeks gestation)
Recurent miscarriage (RM) / Recurrent Pregnancy loss (RPL)
UK: 3 or more pregnancy losses (consecutive or non-consecutive)
EU/USA: 2 or more pregnancy losses
occur in 0.8-1.4% pregnancies
What causes aneuploidy to happen
Oocyte meiotic arrest
oocyte meiotic arrest
Maternal and Paternal homologous chromosomes line up, DNA is replicated, recombination - meiosis suddenly arrested, resumes just before ovulation (up to 50 years later)
Why does aneuploidy increase with maternal age?
Cohesin protiens which hold together chromatids of homologous chromosomes are not replaced
leadng to loss of cohesion
so chromatids can separate and drift during meitotic division rather then accurately segregated by spindle
Two cohesin proteins involved in maintaining cohesion between chromatids within chromosomes
REC8 and SMC2
Ectopic pregnancy
implantation of embryo at site other than uterine endometrium - extra-uterine implantation
- 98% of implantation events occur in fallopian tube (can occur in ovary, cervix ect)
Incidence of ectopic pregnancy
1-1.5% of pregnancies
Treatment of ectopic pregnancy
Expectant management - via chemotherapy (methotrexate)
surgery to remove trophoblast/ tube
rupture can lead to severe internal bleeding
Gestational trophoblastic diseases
e.g Hydatidiform mole
abnormal cells/tissues growing from tissue that forms in pregnancy
two types of hydatidiform moles
complete
partial
Complete hydatidiform moles
fetal tissue absent
Partial hydatidiform mole
fetal tissue present
Incidence of benign hydatidiform moles
1/500 - 1/1500 pregnancies
Malignant gestational trophoblastic diseases
e.g Gestational Trophoblastic Neoplasias
arise following ~20% of cases of hydatidiform mole
Rare gestational trophoblastic neoplasias
invasive mole
choriocarcinoma
Very rare gestational trophoblastic neoplasias
Placental Site trophoblastic tumour (PSTT)
Epithelioid Trophoblastic Tumour
Risk factors of ectopic pregnancy (biological)
Prior ectopic pregnancy
Prior fallopian tube surgery
Certain STIs
Pelvic inflammatory disease
Endometriosis
Environmental risk factors of ectopic pregnancy
Smoking
cannabis smoking
age older than 35
Hx of infertility
use of IVF
Sequence of developmental events in early embryonic development
cleavage
compaction
implantation
gastrulation
neurulation
pre-blastocyst stage, embryos are reliant on mRNAs and proteins stored within the oocyte to complete their earliest stages of development.
What is the name of the developmental event at which the embryo begins to synthesise these factors itself?
Embryo Genome activation / MZT (maternal zygotic transition)
Fallopian tube (oviduct)
facilitates transport of oocyte from ovary to uterus
ciliated epithelial cells line fallopian tube epithelium - cilia beating facilitates embryo movement along tube
How does smoking impact the fallopian tube
Tobacco smoke inhibits cilia function
reduced movement of fluid in fallopian tube
and thus transits of embryo along tube
Continine (alters balance of pro- and anti-apoptosis proteins in fallopian tube), component of cigarette smoke changes levels of PROKR1 in fallopian tube
What regulates the contraction of smooth muscle layer surrounding the fallopian tubes
PROK1 and PROK2 growth factor proteins signal through the PROKR1 and PROKR2 receptor proteins to regulate contractility of smooth muscle
PROKR1 and PROKR2 levels in ectopic pregnancy
Reduced levels in fallopian tubes
How might cannabis use affect the fallopian tube?
Fallopian tube expresses cannabinoid receptors (CB1and FAAH)
THC may act directly on fallopian tube to preturb embryo transit or alter balance of endocannabinoids in tube leading to disrupted embryo environment
