2: Disorders of early development

Question 1

Pregnancy loss can arise from

Answer 1

• 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

Question 2

Miscarriage is

Answer 2

loss of pregnancy prior to 23 weeks gestation

early clinical pregnancy loss (<12 weeks gestation)
Late clinical pregnancy loss (>24 weeks gestation)

Question 3

Recurent miscarriage (RM) / Recurrent Pregnancy loss (RPL)

Answer 3

UK: 3 or more pregnancy losses (consecutive or non-consecutive)
EU/USA: 2 or more pregnancy losses

occur in 0.8-1.4% pregnancies

Question 4

What causes aneuploidy to happen

Answer 4

Oocyte meiotic arrest

Question 5

oocyte meiotic arrest

Answer 5

Maternal and Paternal homologous chromosomes line up, DNA is replicated, recombination - meiosis suddenly arrested, resumes just before ovulation (up to 50 years later)

Question 6

Why does aneuploidy increase with maternal age?

Answer 6

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

Question 7

Two cohesin proteins involved in maintaining cohesion between chromatids within chromosomes

Answer 7

REC8 and SMC2

Question 8

Ectopic pregnancy

Answer 8

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)

Question 9

Incidence of ectopic pregnancy

Answer 9

1-1.5% of pregnancies

Question 10

Treatment of ectopic pregnancy

Answer 10

Expectant management - via chemotherapy (methotrexate)
surgery to remove trophoblast/ tube

rupture can lead to severe internal bleeding

Question 11

Gestational trophoblastic diseases

Answer 11

e.g Hydatidiform mole
abnormal cells/tissues growing from tissue that forms in pregnancy

Question 12

two types of hydatidiform moles

Answer 12

complete
partial

Question 13

Complete hydatidiform moles

Answer 13

fetal tissue absent

Question 14

Partial hydatidiform mole

Answer 14

fetal tissue present

Question 15

Incidence of benign hydatidiform moles

Answer 15

1/500 - 1/1500 pregnancies

Question 16

Malignant gestational trophoblastic diseases

Answer 16

e.g Gestational Trophoblastic Neoplasias

arise following ~20% of cases of hydatidiform mole

Question 17

Rare gestational trophoblastic neoplasias

Answer 17

invasive mole
choriocarcinoma

Question 18

Very rare gestational trophoblastic neoplasias

Answer 18

Placental Site trophoblastic tumour (PSTT)
Epithelioid Trophoblastic Tumour

Question 19

Risk factors of ectopic pregnancy (biological)

Answer 19

Prior ectopic pregnancy
Prior fallopian tube surgery
Certain STIs
Pelvic inflammatory disease
Endometriosis

Question 20

Environmental risk factors of ectopic pregnancy

Answer 20

Smoking
cannabis smoking
age older than 35
Hx of infertility
use of IVF

Question 21

Sequence of developmental events in early embryonic development

Answer 21

cleavage
compaction
implantation
gastrulation
neurulation

Question 22

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?

Answer 22

Embryo Genome activation / MZT (maternal zygotic transition)

Question 23

Fallopian tube (oviduct)

Answer 23

facilitates transport of oocyte from ovary to uterus
ciliated epithelial cells line fallopian tube epithelium - cilia beating facilitates embryo movement along tube

Question 24

How does smoking impact the fallopian tube

Answer 24

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

Question 25

What regulates the contraction of smooth muscle layer surrounding the fallopian tubes

Answer 25

PROK1 and PROK2 growth factor proteins signal through the PROKR1 and PROKR2 receptor proteins to regulate contractility of smooth muscle

Question 26

PROKR1 and PROKR2 levels in ectopic pregnancy

Answer 26

Reduced levels in fallopian tubes

Question 27

How might cannabis use affect the fallopian tube?

Answer 27

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