Sexual Differentiation Flashcards
What is the SRY gene?
Sex determining gene on the Y chromosome
Encodes for a DNA-binding protein that functions as a transcription factor for male testis differentiation
Located close to the pseudoautosomal region on the Y
What are indifferent gonads?
Gonads prior to 7th week of gestation are identical
Composed of external cortex and internal medulla
What are primordial germ cells?
Originate outside of the gonad
Begin migrating from the yolk sac endoderm to the indifferent gonad early in 5th week
What occurs after the PGCs enter the developing genital ridge?
They are rapidly surrounded by cords of somatic cells
The sex chromosomes in these somatic cells determine the type of gonad the genital ridge will become
What is the gene product of the SRY gene and what is its function?
SOX9 transcription factor that is the principal regulator of Sertoli cell differentiation
How are the testis cords formed?
The primitive sex cords penetrate deep into the medulla and form the testis cords
Subsequently, they become separated from the genital ridge by a mesenchymal layer that later becomes the tunica albuginea
What is the first histologically discernable event of testis differentiation?
Appearance of Sertoli Cells in the medulla between weeks 6-7
What are gonocytes?
PGCs transition to gonocytes within the testis cords and enter mitotic arrest at 10-12 weeks
By this time the gonocytes will have differentiated into prespermatogonia
Male germ cells are prevented from entering meiosis until puberty
What are the testis cords?
Precursors to seminiferous tubules
Remain as solid structures until puberty, when the develop a lumen and mature into fully functional seminiferous tubules
What is the role of paracrine factors released by sertoli cells?
Recruiting mesenchymal cells to differentiate into:
Peritbuluar myoid cells
Male-specific vasculature endothelial cells
Leydig cells
What do Leydig cells produce?
Testosterone
Insulin-like 3 (INSL3)
What is the relationship between seminiferous tubules and germ cells?
Presence of germ cells is not a requirement for seminiferous tubule development
What is Klinefelter syndrome?
Males with XXY karyotype caused by nondisjunction
Small, firm testes with hyalinized seminiferous tubules
What three things does the differentiation of an ovary require?
Invasion of the cortex by PGCs
Reactivation of the inactivated X chromosome in germ cells
Absence of the SRY gene
What is Turner Syndrome?
Ovarian disgenesis associated with a 45, X karyotype
What do the PGCs do in ovarian differentiation?
Migrate to presumptive ovary and differentiate into oogonia
At week 11, some of the oogonia will leave the pool of proliferating cells and enter into meiosis (primary oocytes)
When is meiosis arrested in primary oocytes?
Prophase I
What is atresia?
Form of programmed cell death
Occurs to some oogonia when with the onset of oogonial meiosis
What occurs in the ovary after week 13?
Primordial follicles arise as pregranulosa cells affregate to form a single layer of cells around the primary oocyte
What are the three reasons for decline of germ cells in the ovary post-20 weeks?
Decrease in the rate of oogonial mitosis
Atresia of oogonia that are not incorporated into follicles
Atresia of follicles that start to mature
What are cortical cords?
Represent a second wave of cord formation that occurs at week 7
Extend into underlying mesenchyme
PGCs are incorporated into cortical cords and during month three, the cortical cords break up into distinct cell clusters (primordial follicles)
What are primordial follicles?
Primary oocyte surrounded by a single layer of pregranulosa cells
What is the pathway responsible for ovarian differentiation in the absence of SRY?
B-catenin/WNT4
What are the two sets of genital ducts in the undifferentiated reproductive tract of both sexes?
Mesonephric/wolffian ducts
Paramesonephric/mullerian ducts
What do the wolffian ducts differentiate into if they persist?
Epididymis
Vas deferens
Seminal vesicles
Ejaculatory ducts
What do the Mullerian ducts differentiate into if they persist?
Fallopian tubes
Uterus
Cervix
Upper third of the vagina
What hormones are required for male genital tract differentiation and where are they produced?
Anti-mullerian hormone (AMH) - Sertoli cells
Testosterone - fetal Leydig Cells
How does the female genital tract differentiate?
The differentiation of the genital ducts along gemale lines occurs in the absence of hormone stimulation
Most frequently occur uterine anomalies are the result of varying degrees of fusion of the Mullerian ducts
What is syndrome of persistent Mullerian ducts?
Rare condition that can occur when a normal genotypic/phenotypic male cannot synthesize AMH or has a defective receptor
Muellerian duct derivatives are present in inguinal hernias
Testes often fail to descend
What are the common primordial structures that give rise to the external genitalia?
Genital Tubercle -clitoris/glans penis
Genital Fold - ventral folds of penis/labia minora
Labioscrotal Swelling - Labia majora/scrotum
How do indifferent external genital structures undergo differentiation in males?
Requires dihydrotestosterone
Formed from testosterone by 5a-reductase
What is hypospadias?
External genitals of males in the absence of androgen stimulation
Results in ambiguous external genitals or micropenis with an urethral opening located on the ventral surface
How does the urogenital sinus differentiate in males and females?
Males -Prostatic buds develop from the urogenital sinus
Females - lower part of the vagina forms from the walls of the urogenital sinus
What is symptom of complete androgen resistance?
Testes capable of secreting androgens will be present in abdomen
Male and female internal genital tracts are absent
External sexual characteristics are female
What is 5a-reductase deficiency?
Internal genitalia will develop along male lines and external genitalia will be ambiguous
Further masculinization of external genitalia will occur at puberty
What factors promote testes descent?
Insulin-like peptide3
Testosterone
Both produced by Leydig cells
