Genetics - Sex Determination, Abnormalities Flashcards
Describe gametogenesis, starting with week 4 of embryogenesis.
- Week 4: primordial germ cells originate in endoderm of the yolk sac
- Week 6: primordial germ cells migrate to the genital ridge and associate with somatic cells to form the primitive gonad
- Gonads then differentiate into ovaries (default) or testes (if SRY is present)
- Within the differentiated gonads meiosis gives rise to eggs/sperm
Spermatogenesis:
where, how/when
- in seminiferous tubules of the testes
- prior to puberty: primordial germ cells undergo mitosis and line the tubules
- during puberty: spermatogonia (2N) –> 1˚ spermatocytes (2N) –> 2˚ spermatocytes (N) –> spermatids (N; homologues just separate); mature into sperm via capacitation
Oogenesis:
where, how/when
- in ovaries
- prior to birth: oogonium –> 1˚ oocyte –> 2˚ oocyte; meiosis I arrests here
- at ovulation: meiosis I completes
- at fertilization: meiosis II completes; conversion of 2˚ oocyte to egg
Steps of meiosis I and II
- Interphase: DNA replication, chromosomes are at 2N
- Meiosis I: PMAT
*Prophase has several stages:
1) leptotene - chromosomes replicated
2) zygotene - pairs of chromatids pair up and synapse
3) pachytene - can see tetrad (4 chromatids)
4) diplotene - crossing over
5) diakinesis - oogenesis freezes here - Metaphase: nuclear membrane disappears, spindles appear, pairs align on metaphase plate
- Anaphase: chromatids pulled apart by spindles
- Telophase/Cytokinesis: cell division
Meiosis II - same steps, just faster
During which meiosis does nondisjunction occur?
Meiosis I, when the chromosomes align on metaphase plate
*cocaine/environmental exposures during pregnancy will therefore not affect nondisjunction
Describe the embryogenesis of the Mullerian system.
Because there is no AMH produced (by Sertoli cells) in the female, the Mullerian ducts persist and the Wolffian ducts degenerate. Around 6-11 weeks the ducts fuse to form the fallopian tubes, uterus, cervix and upper 2/3 vagina. Reabsorption of the utero-vaginal septum occurs cranially and caudally.
Describe the morphology of the following Mullerian duct abnormalities (MDAs):
Didelphic
Unicornuate
Bicornuate
Didelphic = ducts fail to fuse all the way down
Unicornuate = only one duct forms
Bicornuate (partial or complete) = ridge forms at the top of the uterus where ducts failed to fuse; in complete, extends to cervix
Describe the anatomical and clinical significance of a Unicornuate MDA.
- 1 tube, 1 uterus, 2 ovaries, +/- rudimentary horn w/wo communication to dominant horn
- Ipsi renal abnormalities 40% pts
- Pregnancy can be normal, pre-term labor, or malpresentation (breech)
Describe the anatomical and clinical significance of a Uterus didelphys MDA.
- 2 tubes, 2 ovaries, 2 cervixes, 2 upper vaginas, 2 everything, lower vagina +/- septum
- Renal agenesis on one side
- Pregnancy can be normal or pre-term labor
Describe the anatomical and clinical significance of a Bicornuate MDA.
- has a cleft in external contour of uterine fundus
- often asx, may be partial or complete, +/- vaginal septum
Describe the anatomical and clinical significance of a septate uterus MDA.
- smooth external uterine surface but septated uterus, partial or complete, from failure of the septum to be reabsorbed
- most common MDA
- Pregnancy can be spontaneous loss, implantation area compromised by avascular area (ie, the fibrous septum that’s still present)
Describe the clinical significance of a DES/T-shaped uterus MDA.
- in the 50-60s pregnant women were given diethystilbesterol (DES), a hormone believed to prevent miscarriage, but actually turned out to be a teratogen
- their female children developed uterine abnormalities including T-shaped uterus, which put them at risk for pregnancy loss, as well as increased risk of vaginal clear cell carcinoma
What is Rokitansky Kunster Hauser syndrome?
- complete agenesis of Mullerian structures
- presents with amenorrhea (note there are ovaries so secondary sex characteristics will occur)
- lacks upper vagina, cervix, uterus, or tubes; renal and skeletal abnormalities also present
- treatment: create a neovagina
What is imperforate hymen?
- failure of reabsorption of uterovaginal septum
- presents with amenorrhea, cyclic pain (seems like menstrual cramps, is moody, etc), abdominal mass
- there is also a hematoma form the non-evacuated cycles
- treatment: hymenotomy and hematoma evacuation
