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11. Gonadal Sex Differentiation

𝐒𝐮𝐛𝐬𝐜𝐫𝐢𝐛𝐞 𝗙𝐨𝐫 𝗠𝐨𝐫𝐞 𝗜𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐨𝐧 𝗛𝐞𝐚𝐥𝐭𝐡 👩‍⚕‍ 𝐚𝐧𝐝 𝗠𝐞𝐝𝐢𝐜𝐢𝐧𝐞💉🩺💊 𝐘𝐨𝐮𝐭𝐮𝐛𝐞 :    / @draishwaryakelkar   📌𝗙𝗮𝗰𝗲𝗯𝗼𝗼𝗸 :   / draishwaryakelkar   📌𝗧𝘄𝗶𝘁𝘁𝗲𝗿:   / aishwayadr   📌𝗜𝗻𝘀𝘁𝗮𝗴𝗿𝗮𝗺 :   / clinical.learning   Sex differentiation includes the following distinct sequential stages: genetic, gonadal, hormonal, phenotypic and psychological. At the genetic stage, chromosomal sex is established at fertilization in which XY indicates male and XX denotes female. During the first two months of human gestation, the two sexes develop identically. The gonadal stage is the period during which indifferent gonads develop into either ovaries or testes. The phenotypic stage is induced in response to gonadal differentiation; the internal genital tract and external genitalia develop into characteristic male or female structures.1-4 Gonads appear initially as a pair of longitudinal genital or gonadal ridges at the 4–5th week. Primitive gonads are formed by the proliferation of germ cells, which migrate from the yolk sac and undergo condensation of the underlying mesenchyme in the sixth week. The gonads do not acquire male or female morphological characteristics until the seventh week of development, so they are classified as indifferent.1-4 Mesonephros is primary embryonal kidney, which functions for a short time during the early fetal period (in the fourth week). The mesonephros and mesonephric ducts are derived from intermediate mesoderm. In the 6th week, the mesonephros forms a large ovoid organ on each side of the midline, which is lateral to the gonadal ridges. Laterally, the tubule enters the longitudinal collecting ducts, which are known as the mesonephric ducts. In male embryos, some caudal tubules and the mesonephric ducts persist and participate in the formation of the genital system, while they disappear in females.1-4 Testis If an embryo is genetically male (46,XY), the indifferent gonad differentiates to testes under influence of the SRY gene on the Y chromosome, which encodes testis-determining factor. The primitive proliferating sex cords penetrate deep into the gonadal medulla to form the medullary cords of the testis. Testis cords are composed of primitive germ cells and sustentacular cells of Sertoli derived from the surface epithelium of the mesonephral ducts. Interstitial Leydig cells, which are derived from the original mesenchyme of the gonadal ridge, lie between the testis cords. The mesonephric ducts persist and form the main genital ducts of male embryo. The efferent ductules represent the remaining parts of the mesonephric system excretory tubules. These link the rete testis and mesonephric duct, which become the ductus deferens. The seminiferous tubules join to the rete testis tubules, which in turn enter into the ductuli efferentes.1-4 Ovary In female embryos with a 46,XX sex chromosome complement, primitive sex cords dissociate into irregular cell clusters. These clusters, which contain groups of primitive germ cells, occupy the medullary part of the ovary. Later, they disappear and are replaced by a vascular stroma that forms the ovarian medulla. These cords split into isolated cell clusters, which each surround one or more primitive germ cells. Germ cells subsequently develop into oogonia, while the surrounding epithelial cells, descendants of the surface epithelium, form follicular cells.1-4 According to Alfred Jost (1976), sex differentiation depends upon testosterone influenced virilization on the mesonephral ducts, urogenital sinus and external genitalia. Jost resolved the controversy surrounding the mechanism of somatic sex differentiation by establishing that male characteristics must be imposed on the fetus by the testicular hormones testosterone and MIS, respectively, which are responsible for the virilization of the mesonephral ducts, urogenital sinus and external genitalia as well as for regression of the Mullerian ducts.4 In the absence or inactivity of these hormones, the development of the fetus is stalled at an indifferent stage; thus, it becomes phenotypically female. By the eighth week of gestation, Leydig cells of the testes begin to produce testosterone and the testes can influence sexual differentiation of the genital ducts and external genitalia. Formation of the external genitalia is completed by the 12th week.