Reproduction 1 - introduction Flashcards
What is the gene on the Y chromosome that determines whether a testes or ovary will be made
SRY gene - sex determining region Y (or testes determining factor) - this is a TF and main target is SOX9 gene
How many X chromosomes are required for normal ovary production
2
If you have only 1 x chromosome what happens to the ovaries
no gonads at all, just fibrous tissue
what do mesenchymal cells develop into
androgen producing cells (does not happen in ovaries)
When do primordial germ cells migrate to gonadal ridge
5-6 weeks into gestation
Is the primordial gonad specific to testes or ovary generation
no
What drives expression of testes
SRY and SOX9
what drives expression of ovaries
lack of SRY
Expression of RSPO1 and WNT4
RSPO1
testes repressor
Gametes and reproductive cells intestes
Gamete-sperm
Reproductive cells- sertoli cells
leydig cells
Gametes and reproductive gonad cells in ovaries
Gametes are ova, then you have follicular cells which can be broken into granulosa and thecal cells. The gametes and ova together make the follicle
What do sertoli cells secrete in development that helps drive male gonadal development
antimullerian hormone
Leydig cells - what do they secrete that will help drive male gonad production
Testosterone - converted in peripheral tissues via DHT via 5-alpha-reductase or estrogens via aromatase
What two things make up a follicle
follicular cells and gamete (ova)
Two types of follicular cells
Granulosa cells, thecal cells
what do granulosa cells make that is important for maturation of gametes
estrogens and progesterone
DHT role in male gonad development
External male genetalia
Testosterone role in male genetial/gonad development
internal male genetalia (wolffian duct)
How do testes induce regression of mullerian duct
secretion of AMH and inhibin B
How do testes induce generation of male internal and external genetalia
Leydig cells produce testosterone and DHT, which form male internal genetalia from Wolffian duct (top - epididymis, middle, ductus deferens, base is seminal vesicle and ejaculatory duct). DHT will also help form prostate and external genetalia
What part of primordial gonad becomes internal male genetalia
medulla
What induces regression of wolffian ducts?
absence of testes (NOT presence of ovary) – no AMH, no androgens.
how do mullerian ducts differentiate
top - fallopian tubes
middle- fuses to become uterus
bottom-cervix and upper 1/3 of vagina
What is internal vs external genetalia for vagina
upper 1/3 - internal genetalia
bottom 2/3 - external genetalia
What part of the primordial gonad develops into internal female genetalia
cortex
urogenital sinus
ventral part of cloacca. In males, separated into 3 regions that develop into bladder, prostatic urethra, and penile urethra. In females, common opening splits into lower 2/3 of vagina and urethra.
Penis, scrotum, and prostate all require what to develop?
DHT
Taking what hair medication might inhibit male external development, and why?
Propecia - it inhibits 5-alpha reductase, so you don’t get formation of external genetalia (no DHT)
When male germ cells divide how many do we end up with at end of meiosis II?
4
When female germ cells divide how many do we end up with at end of meiosis II
1
In females does mitosis of germ cells continue after birth?
nope
Female production of germ cells
no mitosis after birth, jsut have primary oocytes at diploid stage and arrested halfway through meiosis I until puberty when you resume meiosis I. Then you get haploid cells that are arrested but instead of splitting into 2 we get 1 polar body and just goes away. Then you get meiosis 2 arrested halfway through until fertilization.
Disorders of sexual determination - what would this be?
sex chromosome aneuploidy (like turner syndrome, XO, or klinefelter syndrome (XXY )
Disorders of gonadal dysgenesis would be what?
abnormal testes formation in utero - like androgen resistance due to loss of x linked androgen receptor
Disorders of sexual differentiation would be what?
Defects in internal and/or external genetalia like enzyme deficiencies or androgen excess.
What kind of categories of disorders of sexual development can gonadal dysgenesis be seen in?
all of them
Turner syndrome - genotype, results
XO
Streak gonad (cannot form full ovary) No AMH (no testes) - so well developed mullerian duct, you do have female internal genetalia. No testes, so no testosterone - regressed wolfian duct due to no testosterone to develop Phenotypically we have no DHT, so female external genetalia
Klinefelter syndrome - genotype, results
nondisjunction in meiosis leads to XXY
Dysgenetic testes - you get RSPO1 which is a testes repressor, so even though you have Y chromosome you get fighting between X’s and Y’s. However, usually you still get a regressed mullerian duct and developed wolffian. But the result of testes will be quite fibrous
Loss of androgen receptor - genotype, cause, result
X chromosome has the androgen receptor - if receptor is not present, body cannot respond to androgens. Therefore you have no female internal genetalia, testosterone made by leydig cells though will not give internal male genetalia, either - so you get no internal genetalia at all. External genetalia will be female (no androgen recetpor)
Loss of 5-alpha reductase - genotype, cause
Chromosomal XY - testes will have AMH being formed so regression of mullerian duct. Testosterone is made, so wolfian duct will develop. But testosterone will not make DHT, so genetalia will not form properly. Ambiguous - testosterone causes cliteromegaly so it will look like penis is forming but no penis, prostate, or scrotum fully develops
Can also be caused by exposure to propecia
What are some other symptoms of turner syndrme?
Phenotypic issues due to aneuploidy like webbed neck, lymphedema, low set ears, wide set nipples, cubitus valgus).
What are some other telltale symptoms of klinefelter syndrome
Testosterone is low, micropenis, eunuchroid body, lower segment is greater than upper segment by more than 2 inches but slhort arms. Gnecomastia as well due to elevated estradiol and breast development. Systemic phenotypic issues due to aneuploidy. These individuals will also be infertile
In individuals with complete androgen resistance what are hormone levels like?
androgens high (lack of feedback), estrogen levels high (for male). Gonadotropins are high which stimulates more and more androgen production and this will be converted into estrogen since androgen receptors don’t work.
Phenotype is female with blind pouch vagina. High high estrogens and induction of female characteristics.
NO internal genetalia, like, at all
Gonadal dysgenesis - genotype, reasons, result
XX karyotype but possible SRY translocation or loss of RSPO1 gene. No spermatogenesis because other Y chromasome genes not present, ambiguous genetalia, urethra does not exit in proper location
What can be a result of taking contraceptives in pregnancy
Virilization of female XX genotype due to excess ndrogens
