Disorders of early development

Question 1

Is pregnancy loss common in humans?

Answer 1

Yes

errors in embryo fetal development
failure of embryo to implant in the uterine lining
inability to sustain development of an implanted embryo

Question 2

What is early clinical pregnancy loss?

Answer 2

<12 weeks gestation

in the first trimester

Question 3

What is late clinical pregnancy loss?

Answer 3

> 24 weeks gestation

in 2nd trimester until

Question 4

Is miscarriage spontaneous?

Answer 4

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

Question 5

What proportion of conceptions are lost before the pregnancy is detectable by ultrasound scan?

Answer 5

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%

Question 6

What is the major cause of early pregnancy loss?

Answer 6

• 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

Question 7

Why odes aneuploidy increase with maternal age?

Answer 7

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

Question 8

What signalling pathways might underpin RPL/RM * (Recurrent pregnancy loss , Recurrent miscarriage)

Answer 8

Normal embryo development but failed implantation in Lif-deficient mouse models

Reduced levels of LIF in the uterine secretion of subfertile women

Question 9

What is the non selective uterus hypothesis in RPL?

another hypothesis alongside LIF pathway trying to explain trends seen in subfertile women with RM

Answer 9

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)

Question 10

Wat is genomic imprinting?

Answer 10

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

Question 11

What are gestational trophoblastic diseases?

Answer 11

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

Question 12

Give examples of malignant gestational trophoblastic neoplasias?

Answer 12

Invasive mole
Choriocarcinoma

Placental site trophoblastic tumour

Epithelioid trophoblastic tumour

Question 13

How do complete and partial hydatidiform moles arise?

Answer 13

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

Question 14

What is the NLRP7 mutation?

Answer 14

may underly recurrent hydatidiform moles

Question 15

What is ectopic pregnancy?

Answer 15

implantation of embryo at site other than uterine endometrium

1-1.5% pregnancies

rupture can lead to severe internal bleeding

Question 16

Where do ectopic pregnancies happen?

Answer 16

98% at fallopian tube

others are ovary, cervix, other-intra abdominal

Question 17

What are the treatments available for ectopic pregnancy?

Answer 17

chemotherapy - methotraxate, expectant management, , surgery to remove trophoblast / tube

Question 18

risk factors of ectopic oregnanac?

Answer 18

• Recurrent - if had before
• Maternal age increasing
• smoking (mother)
• cannabis (mother)

Question 19

how might cigarrette smoking increase risk of ectopic pregnancies?

Answer 19

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

Question 20

How does cannabis use affect fallopian tube?

Answer 20

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

Question 21

Describe androgenetic and parthenegenetic embryos?

Answer 21

androgenetic embryo - overgrown disorganised placenta
Parthenogenetic embryo - too small placenta bigger embryo. Both leading to early embryo lethality

( genetic imprinting ) tutorial slides,

Question 22

Explain cannabinoid receptors in the fallopian tube?

Answer 22

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