Exam 4 Lesson 23 Gonadal Development Flashcards
The Jost paradigm for sexual differentiation
Chromosomal sex –> Gonadal sex –> phenotypic sex
An XX SRY+ mouse will have what kind of Gonadal development and phenotype?
Testis development and a male phenotype
How does intermediate mesoderm become indifferent gonads?
WT1 and SF-1
How does indifferent Gonads become ovary? Testis?
Ovary –> DAX-1
Testis –> SRY, SOX9
What does DAX-1 inhibit?
SRY and SOX9
What does testis differentiate into?
Sertolli Cells and Leydig cells
What is AMH?
Anti-mullerian hormone
From Sertolli cells to AMH?
WT1 and SF-1
From AMH to Mullerian Duct Regression
AMH-R
From Leydig cells to testosterone?
SF-1
From testosterone to D?
5alpha-R
From testosterone to epididymis, vas deferments and seminal vehicles?
AR
From D to pens, scrotum and prostrate?
AR (androgen receptor)
D
dihydrotestosterone
5alphaR
5 alpha reductase
What is SRY? What is it responsible for?
A sex determination gene on Y chromosome. Responsible for male differentiation.
What does DAX-1 support?
Female characteristics
What is FOXL2 gene responsible for?
Ovary development and maintenance
What is visible in genital system at five weeks?
Primordial germ cells, gut endoderm, urogenital ridges, pronephros, aorta, notochord, neural tube
What is visible in genital system at six weeks?
wolffian duct, mnullerian duct and indifferent gonad
What differentiates in the male genital system?
seminiferous tumbles differentiate and show spermatogonia and Sertoli cells. The steroidogenic Leydic cells appear between the tumbles and the Mullerian duct regresses.
What differentiates in the female genital system?
Primordial follicles consisting of an oocyte and flattened surrounding cells appear and the Wolffian duct regresses.l
When are both Wolffian and Mullerian ducts present?
In the indifferent stage
What happens during the differentiation of the female genital ducts?
In the absence of testicular hormones, the Mullerian ducts develop into the Fallopian tubes, the uterus and the upper section of the vagina. The Wolffian duct regresses.
What happens during the differentiation of the male genital ducts?
Testosterone virilizes the Wolffian ducts to form the rate test is, epididymis, vas deferments and seminal vehicle. In addition, due ot the secretion of anti-Mullerian hormone from the Sertoli cells, the Mullerian ducts regress.
What is the embryonic genital ridge?
Formation of primitive sex cords from migrating primordial germ cells and mesoderm
What makes up the embryonic genital ridge?
The aorta feeds into Mesonephric duct (Wolff). Under the mesonephric duct is the paramesonephric duct (Müller). At the other end are the primordial germ cells, under the aorta globe. In the middle are the primitive sex cords and the proliferating coelomic epithelium.
What ducts are present when testes develop?
Both. Paramesonephric duct (Mullerian) will degenerate.
How do testes develop?
The mesonephric tubule turns into the ductus deferments with excretory mesoneophric tubule. The coelomic epithelium and primitive sex cords turn into the horseshoe shapes testis cords and the tunica albuginea and the rate testis cords
What develops in later stage of testes development?
The excretory mesonephric tubule become epigenital and paragenital tubule. THe paramesonephric tubercle develops.
What is the genital tubercle?
It is the bipotential primordium that forms in front of the urogenital slit.
What must be absent for female genitalia to develop?
5alpha-dihydrotestosterone
What develops in the absence of 5alpha-dihydrotestosterone?
A clitoris develops from the genital tubercle, as well as labioscrotal dwellings that become the labia majors and labia minors.
What develops when 5alpha-dihydrotestosterone is present?
The genital tubercle turns into a pens and the fusion of the labioscrotal dwellings form the scrotum, into which the testes will descend.
How is testosterone reduced to dihydrotestosterone?
5alpha-reductase
What ducts are present during the development of the ovary?
Two ducts still present. Wolffian duct will degenerate.
What is the epoophoron?
part of female internal genitalia. remnant of Wolffian duct.
Male reproductive system develops from the …?
mesoderm
In development of male reproductive system, when does germ cell migration take place?
Weeks 4-6 of gestation
At what point do Sertoli cells appear? Leydig cells?
7 weeks and eight weeks respectively
In male rep. System devt, When does Mullerian duct regression happen?
From weeks seven to 11.5
In male rep. System development, when does Wolffian duct stabilization happen?
Weeks eight to 12.
In male rep system development, when is there male external genital differentiation?
Weeks 9 to 13
In male rep system development, when do testosterone levels rise?
Rise from weeks 9 to 11, plateau from 11 to 14.5, fall from 14.5 on.
In male rep. System development, when to testes descend?
Weeks eleven to 40
In male rep system development, when is there external genital growth?
From weeks 13 to 40.
Path from urogenital ridge to female or male reproductive system?
A. urogenital ridge
b. bipotential gonads with wolffian ducts and mullerian ducts
c. sex discrimination with SRY
d. positive SRY leads to degeneration of Mullerian ducts
e. positive SRY leads to test is, leydig and sertoli cells.
f. Leydig cells product testosterone and INSL3 and lead to prostate and pens growth, fusion of labioscrotal folds and testicular descent.
g. sertoli cells leads to MIS
If no SRY, the Mullerian ducts do not regenerate and we get female organs
How do Sertoli cells regress Mullerian duct?
With AMH
What leads to Wolffian duct differentiation?
Release of testosterone and INSL3 from Leydig cells
How do male testosterone levels differ at different stages of life?
A. high in second trimester of gestation period
b. drop at birth
c. high in first year of life
d. low from years 1 to 10
e. rising during pubertal stage
f. plateau in adulthood
g. fall in old age
How do events for female and male sexual differentiation differ?
Both male and female development experience germ cell migration at week 5.
At week 6, males also experience spermatogenic cords and sertoli cells, which release AMH, which causes Mullerian duct regression
Mullerian duct regression leads to testosterone synthesis, differentiation of the external genitalia and wolffian duct differentiation
A lack of AMH causes female differentiation.
What happens during female sexual differentiation?
Estrogen synthesis begins at week 8 and rises to plateau between weeks 10 and second trimester. Wolffian duct degenerates. There is uterine and vaginal development. Ovarian follicles form and increase in second trimester.
How do female germ cells change in number as a woman ages?
7 million peak at 7 months of gestation, when first melodic arrest happens.
Levels decrease to 2 million at birth. Decrease to 400,000 fertile cells at puberty, decrease to zero at menopause.
What does puberty signify?
The transition from a non-reproductive state into a reproductive state.
What happens during puberty?
Widespread endocrine changes like adolescent growth spurt, skeletal changes, increase in muscle and fat tissue, maturation of sex organs, and profound psychological changes.
What does endocrinology of human puberty consist of?
adrenarche and gonadarche, which are independently regulated
adrenarche
The increase in androgen secretions from the zonal reticularis of the adrenal cortex that occurs between the ages of about 6 to 8 years
gonadarche
Occurs years after adrenarche, refers to the activation of Gonadal sex steroid production
In females, which gonadotropin has higher levels during neonatal and prepubertal phases?
FSH levels are greater than LH and pulsatile secretion of LH is minimal
What gonadotropin are secreted in females as puberty approaches
LH secretion increases during sleep
What happens to gonadotropin in females once puberty is completed?
LH secretion is greater that FSH secretion and cycle gonadotropin release occurs.
What happens with hormones at menopause?
Cyclic gonadotropin release ceases and plasma levels of both gonadotropin increase.
What central events lead to initiation of puberty?
A. GABA and EAA neurons are instrumental in onset of pulsatile release of LHRH and onset of puberty
B. Lepton and IGF-1 signaling contributes to onset of puberty
What does GABA do in puberty?
GABA neurons inhibit rise of EAA neurons. GABA neurons inhibit NE, NPY and other stimulatory neurons and thus inhibit LHRH neurons
What do EAA neurons do in puberty?
A rise in EAA neurons leads to:
A. NE, NPY and other stimulatory neurons and to LHRH neurons
B. Leads to increase in astroglial cells and PGE2, and an increase in LHRH neurons.
C. an increase in LHRH neurons leads to puberty
What do lepton and IGF-1 do in puberty?
Lepton stimulates NE, NPOY and other stimulatory neurons, which stimulate LHRH neurons.
IGF-1 stimulates LHRH neurons directly.
Stages of gonads development male vs female
Gestational age 0 , bipotential gonads
37-45 days seeded with primordial germ cells
At 43-50 days, male, seminiferous tubule develop, and test is. At sixty days, Leydig cells.
If no male development, at 80 days there is onset of mitosis. At 120 days, ovarian organogenesis. Between 20 and 25 weeks, primary follicles and stroma
Stages of genital tract development
At 43-50 days, if mullerian ducts regress, female ducts. If not, male.
Past sixty days, Estrada genitalia either becomes pens then or waits becomes female genitalia at 11-12 weeks. Past 60 days, urogenital sinus, becomes prostate then, or then undergoes vaginal organogenesis and becomes vagina at 20-25 weeks.
What does loss of germ cells during migration to or after seeding of indifferent gonads in a 45, X individual lead to?
A Gonadal streak, because germ cells are necessary for ovarian devt of the indifferent gonads.
When does loss of germ cells happen?
After implantation of germ gells
What happens in the presence of 45,X/46,XX mosaicism
Gonadal differentiation may vary from that of an ovary to that of a Gonadal streak
What happens in 45,X/46, XY?
Depending on the sex chromosome constitution of the germ cells and Gonadal blastoma, Gonadal differentiation may vary from that of a testis to that of a Gonadal streak.
What happens in 47,XXY individuals?
Germ cells become implanted in the primitive test is, but a marked loss of spermatogonia seems to occur in the perinatal period and infancy.
XX leads to
ovary
XO loads to
Gonadal streak
XY leads to
testis
XXY leads to
testis
What is Turner Syndrome?
45,X Gonadal Dysgenesis
Turner Syndrome Karyotype and inheritance
Karyotype: 45, X
Inheritance: melodic or mitosis nondisjunction
Turner Syndrome Genitalia and duct derivatives
Genitalia: Female
Wolffian duct derivatives: absent
Mullerian duct derivatives: normal female
Turner Syndrome gonads, habits and hormone profile?
Gonads: streak
Habitus: short stature; sexual infantilism at puberty; somatic stigmata
Hormone profile: increased plasma LH and FSH concentrations; decreased plasma estradiol levels
Klinefelter syndrome Karyotype and inheritance
Karyotype: 47, XXY
Inheritance; sporadic, assoc. with advanced maternal age; nondisjunction during first or second melodic division in either parent. Mitosis nondisjunction.
Klinefelter syndrome genitalia and duct derivatives
Genitalia: male
Wolffian: normal
Mullerian: absent
Klinefelter syndrome Gonads, habits and hormone profile?
Gonads: small, firm testes; seminiferous tubule dysgenesia, azoospermia, leydig cell hyperplasia
Habitus ; poor to normal civilization at puberty: gynecomastia; disproportionately long legs
Hormone profile: testosterone levels variable but usually decreased; increased levels of plasma LH and FSH postpubertally
