Disorders of early development Flashcards
Is pregnancy loss common in humans?
Yes
errors in embryo fetal development
failure of embryo to implant in the uterine lining
inability to sustain development of an implanted embryo
What is early clinical pregnancy loss?
<12 weeks gestation
in the first trimester
What is late clinical pregnancy loss?
> 24 weeks gestation
in 2nd trimester until
Is miscarriage spontaneous?
In some cases
It can also be RECURRENT:
defined at 3+ failed pregnancies not consecutive
should be able to either detected HCG or fetal heartbeat
What proportion of conceptions are lost before the pregnancy is detectable by ultrasound scan?
30% conceptions lost prior to implantation
30% following implantation but before the missed menstrual periods
Clinical pregnancy loss increases with age, 10% in 20-24
50 in 40-44%
What is the major cause of early pregnancy loss?
- aneuploidy in embryos
53% of embryos created by using donor eggs in IVF are aneuploid
50% of lost early pregnancies display chromosomal error
exponential increase in risk of trisomic pregnancy with increasing maternal age
Why odes aneuploidy increase with maternal age?
through F meiotic arrest, chromatids of homologous chromosomes held together by cohesion proteins
these proteins are no replaced and loss of cohesion proteins between chromatids increases the age of the oocyte
this loss results in the chromatids separating and drifting during meiotic division, rather than being segregated accuratley by the spindle
What signalling pathways might underpin RPL/RM * (Recurrent pregnancy loss , Recurrent miscarriage)
Normal embryo development but failed implantation in Lif-deficient mouse models
Reduced levels of LIF in the uterine secretion of subfertile women
What is the non selective uterus hypothesis in RPL?
another hypothesis alongside LIF pathway trying to explain trends seen in subfertile women with RM
uterus highly permissive of embryo implantation and so lose selectivity in embryo quality
changes in uterine mucin Expression in women with RM/RPL ( which are involved in the selectivity)
Wat is genomic imprinting?
Some genes only expressed from paternally inherited copy : telling developing embryo to take resources from the mother
some genes only expressed from maternal copy : telling embryo to conserve resources from body for future pregnancy
intergenomic conflict
Can lead to molar pregnancy and gestational trophoblastic diseases
What are gestational trophoblastic diseases?
collection of disorders characterised by growth of trophoblastic tissue
e.g.
benign : hydatidiform moles:
–> complete hydatidiform mole : fetal tissue is absent
–> partial hydatidiform mole : fetal tissue present
Give examples of malignant gestational trophoblastic neoplasias?
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
Epithelioid trophoblastic tumour
How do complete and partial hydatidiform moles arise?
complete hydatidiform moles: empty egg fertilised by sperm which then duplicates for total chromosome number. OR two sperms for full set of chromosomes
partial hydatidiform moles: normal egg fertilised by 1 sperm which then duplicates its genetic material or 2 sperms fertilise.
- molar pregnancies have a grape like villi present large placenta - linked with the paternal genes need to use mothers resources
What is the NLRP7 mutation?
may underly recurrent hydatidiform moles
What is ectopic pregnancy?
implantation of embryo at site other than uterine endometrium
1-1.5% pregnancies
rupture can lead to severe internal bleeding
Where do ectopic pregnancies happen?
98% at fallopian tube
others are ovary, cervix, other-intra abdominal
What are the treatments available for ectopic pregnancy?
chemotherapy - methotraxate, expectant management, , surgery to remove trophoblast / tube
risk factors of ectopic oregnanac?
- Recurrent - if had before
- Maternal age increasing
- smoking (mother)
- cannabis (mother)
how might cigarrette smoking increase risk of ectopic pregnancies?
Cotinine in smoke, regulates expression of PROKR1 which regulates fallopsian tube smooth muscle contractility
Cotinine also induced pro-apoptosis protein expression in fallopian tubes
tobacco smoke inhibits ciliary function –> reduce tubul transit to embryo
How does cannabis use affect fallopian tube?
fallopian tube expresses cannabinoid receptors CB1
CB1 levels are reduced in ectopic pregnancy patients
endocannabinoids levels are elevates in ectopic pregnancy fallopian tubes
componants such as THC in cannabis may act directly on tube or peturb embryo transit
OR
alters balance of endocannabinoids the ‘endocannabinoid tone’ in the tube leading to a distrupted embryo environment
Describe androgenetic and parthenegenetic embryos?
androgenetic embryo - overgrown disorganised placenta
Parthenogenetic embryo - too small placenta bigger embryo. Both leading to early embryo lethality
( genetic imprinting ) tutorial slides,
Explain cannabinoid receptors in the fallopian tube?
If there r receptors there is a role in normal physiology
in mice it was seen without the receptor the mouse would get ectopic pregnancy
use of exogenous cannabis can distrupts the signalling so has an impact like there is less cannaboid effect hence why using more cannabis causes distruptive impact on the cannaboid signalling causes low levels causes ectopic pregnancy * not causing its more of a correlation
