Editing Undescended Testicle (section)

== Embryology of Testicular Development ==

=== Differentiation of the Testis ===
* '''<span style="color:#ff0000">Gonads are first identified at 32 days (≈4.5 weeks)''' in humans.
** '''<span style="color:#ff0000">At this sexually indifferent stage, the gonads and the internal and external genitalia are identical in males and females.'''
** '''<span style="color:#ff0000">Gonadal determination involves separate genetic pathways for development of testis and ovary.'''
*** '''<span style="color:#ff0000">SRY (sex-determining region on the Y chromosome) is a master switch in males that regulates downstream testis-determining genes.'''
* '''<span style="color:#ff0000">By 6 weeks’ gestation, primordial germ cells</span>''' migrate from the yolk sac and '''<span style="color:#ff0000">differentiate into gonocytes</span>'''
* '''<span style="color:#ff0000">In males, expression of SRY begins at 41 to 44 days (≈6 weeks) followed by the histologic appearance of Sertoli cells'''
** '''<span style="color:#ff0000">SRY expression in the indifferent gonad triggers testicular development.'''
** SRY is important for Sertoli cell specification, but downstream testis-determining genes are required for Sertoli cell differentiation and proliferation
* '''<span style="color:#ff0000">Fetal Sertoli cells produce anti-müllerian hormone (AMH) (also called müllerian inhibiting substance [MIS]) soon after they differentiate'''
** Fetal and early postnatal Sertoli cells lack androgen-receptor expression.
*** Precense of androgen-receptor on Sertoli cells would allow inappropriate androgen-induced inhibition of AMH production and precocious stimulation of spermatogenesis.
** '''<span style="color:#ff0000">The process of müllerian regression occurs at 9 to 10 weeks'''
*** The early development of the external genitalia in the two sexes is relatively similar before the 9th week of gestation.
** '''AMH levels remain high during childhood and are downregulated at puberty.'''

=== Testicular Hormone Production ===
* Critical for masculinization of the reproductive tract and testicular descent
* '''In the fetus, Leydig cell development is divided into 3 phases:'''
*# '''Proliferation and differentiation phase at 7-14 weeks’ gestation'''
*# '''Maturation phase until 18 weeks’ gestation'''
*# '''Involution phase that continues until term'''
* '''<span style="color:#ff0000">Synthesis of testosterone by fetal Leydig cells starts as early as 6 to 7 weeks’ gestation and appears to be initially independent of gonadotropin stimulation.'''
** '''Placental human chorionic gonadotropin (hCG) stimulates a peak in androgen production by fetal Leydig cells at 14-16 weeks, and the testis then becomes responsive to fetal luteinizing hormone (LH)'''
* '''<span style="color:#ff0000">At 9-13 weeks of gestation, dihydrotestosterone (DHT) simulates androgen receptors in the'''
*# '''<span style="color:#ff0000">Genital tubercle to differentiate into penis'''
*# '''<span style="color:#ff0000">Urethral folds to differentiate into the ventral aspect of penis'''
*# '''<span style="color:#ff0000">Labioscrotal swellings to differentiate into scrotum'''
*#* '''Also known as genital swellings or labioscrotal folds'''§
*#* The labioscrotal swellings are first visible at 7 weeks and fuse by 10-12 weeks
* '''<span style="color:#ff0000">By the end of the first trimester (12 weeks), the external genitalia are completely masculinized'''
* '''Locally produced estrogen may play a role in testis development'''