Test 3: 57 Flashcards
Androgen insensitivity syndrome
(Testicular feminization) intersex
X-linked recessive condition in 46,XY karyotype
Caused by the mutation of androgen receptor
Patient’s body do not respond to androgens (e.g., testosterone, dehyrotestosterone)
genetically male, no internal genitalia (neither male or female inside), external female
AIS will have what internal genitalia?
neither, male or female
both wolffian and mullerian ducts get knocked out
AIS will have what external sex organs
Androgen insensitivity syndrome
female
puberty → will develop breast due to aromatization of testosterone to estradiol
how will AIS produce breasts
aromatization of testosterone to estradiol during puberty
Persistent Müllerian duct syndrome (PMDS)
- Autosomal recessive congenital disorder
- Mutation in AMH or AMH receptor (MISRII)
- Reported in Miniature Schnauzwer dog
- ~25% career, ~2% affected
XY with normal testis, will have both sex ducts because anti-mullerian hormone doesn’t work so will have wolffian and mullerian ducts
PMDS will have what internal genitalia?
genetically male
anti-mullarian hormone doesn’t work and mullerian duct will persist. Will also keep Wolffian duct because testosterone still there
both male and female internal organs
Freemartinism
male and female twins in cows with shared blood supply
females usually have small or no female internal organs and sometimes male internal organs due to anti-mullerian hormone and testosterone from male fetus
females will be XX/XY chimeria
indifferent gonad or bipotential gonad are made of what types of cells
gonadal somatic cells (intermediate mesoderm derivatives)
primordial germ cells (epiblast)
gonadal somatic cells and germ cells have ___ origins
different
gonadal somatic cells can turn into what
sertoli cells by SOX9 (male) and Granulosa FOXL2 (female)
Interstitial
interstitial cells + sertoli cells =
leydig and other interstitial cells
interstitial cells + granulosa =
theca, and other interstitial cells
male gonad express what transcription factor to change into testis
SRY
what does SRY do?
change into testis
SRY→ SOX9→ FGF9, anti mullerian hormone and Cyp26B1
FGF9→ testosterone synthesis from leydig cells
Cyp26B1 → spermagogenesis
how does SRY effect females
SOX9 will inhibit Rspo1
FGF9 will inhibit Wnt4
how will lack of SRY effect ovary?
Rspo1 will inhibit Sox9
Wnt4 will inhibit FGF9
what genes lead indifferent gonad to ovary?
negative SRY
Rspo1→ Wnt4 and b-catenin → Foxl2
XX ovotesticular DSD
true hermaphroditism
- XX/XY Mosaicism
- Translocation or duplication of a small portion of chromosome containing SRY, SOX9, or FGF9 gene
- Mutation in RSPO1, Wnt4 etc..
DSD
disorder of sex development
disorder of sex development
atypical sex
congenital condition
chromosomal
XO turner syndrome, XXY klinefelter, XX/XY chimera
gonadal
46 XY gonadal dysgenesis
46, XY ovotesticular DSD
46,XX testicular DSD
non-gonadal
–Disorders in androgen synthesis or action
–Androgen excess etc
•___ induces meiosis in female PGCs(feature of oogenesis)
Retinoic acid
•Retinoic acid produced by mesonephros is metabolized by ___ produced by male testis (Sertoli cells).
Cyp26b1
no retinoic acid = no meiosis = no female PGCs = prospermatogonia
___ plays critical role in determining brain sex (CAIS vs control XX female)
Androgen
preimplanation genetic diagnosis
pre select healthy before implanting
genome engineering
CRISPR/ CAS9
can fix DNA
why does sex determination clinically matter?
diseases can be sexed linked
reproduction
most DSD are infertile
Ovaries and testes are essential for __ and ___ formation
oocyte and sperm
germ cells and niche cells work together to form haploid cells
professors research
Using the BTAG lines, we now tested numbers of cytokine conditions to maximize the induction efficiency of BT and AG double positive cells. And we established the most robust induction system where we first induce hIPSCs into incipient mesodermal like cells, iMeLCs, which then further induced into hPGC-like cells by culturing these in aggregates in the presence of BMP4, SCF, EGF, and LIF.
