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Gonadal Development In The Embryo

Gonadal Development In The Embryo
Role of sex chromatin in reproductive development
All mammalian females are homogametic and represent the “default” pathway in sexual differentiation. Homogametic describes the sex whose cell nuclei contain two similar sex chromosomes. While this characterizes mammalian females, the homogametic sex is male in butterflies, birds and some amphibians and fishes. In humans, all normal oocytes from genetic females will carry 22 autosomes and an X chromosome (22X). Mammalian embryos of both genetic sexes are bathed in relatively large amounts of placental estrogen during development. In the absence of specific factors regulated by a single gene on the Y chromosome, embryos will develop into a female phenotype. The human female, like all mammalian females, represents the fundamental or undifferentiated phenotypic sex.

Gonadal Development In The Embryo, Role of sex chromatin in reproductive development,

All mammalian males are heterogametic. They produce gametes with both 22X and 22Y chromosome complements. Males are considered the differentiated phenotypic sex. With few exceptions, any individual that carries a specific piece of the Y chromosome will develop a testis and a male phenotype. This segment of the Y chromosome has been called the sex-determining region of the Y chromosome (SRY) (Fig. 5.1). Specific instruction from the SRY region of the Y chromosome directs the undifferentiated gonad to become a testis. Without the presence of SRY, a fetus will develop along the default or female phenotypic pathway.
The Y chromosome is much smaller than the X and very little of its DNA is available for RNA synthesis. Many of the genes that control testicular development from the undifferentiated gonad are therefore located on other chromosomes, including autosomes and the X chromosome. However, the Y chromosomecontains a specific, single-copy gene that determines testicular differentiation. This gene is located on the short arm of the chromosome within SRY and appears to activate genes on other chromosomes.
Evidence for the importance of SRY comes from both clinical and experimental research results. Examination of the DNA sequences of women with XY karyotypes has revealed that a single locus within the Y chromosome must be present and intact for an individual to have a testis. Absence of, or damage to, this DNA sequence in individuals with an otherwise intact 46XY male chromosomal content results in ovarian development and a phenotypic female. Likewise, examination of the DNA sequences of phenotypic men with XX karyotypes will reveal the aberrant presence of SRY sequences.

Gonadal Development In The Embryo, Role of sex chromatin in reproductive development,

Gonadal differentiation
Gonadal development begins in the human at the 4th embryonic (6th menstrual) week in parallel with the formation of the ventral body wall. The first step in gonadal development is the migration of undif- ferentiated primordial germ cells from their site of formation in the yolk sac. These germ cells arise from the endoderm lining the yolk sac; they detach themselves and migrate dorsally along the yolk stalk, midgut and dorsal mesentery to reach the genital ridges. The genital ridges lie on the medial aspect of the mesonephric ridge that will contribute to the developing kidney. Over the next 2 weeks the primordial germ cells mitose repeatedly, forming a vast population of precursor gametes. Failure of these germ cells to develop and populate the genital ridges at this time will result in complete failure of gonadal formation.
When germ cells reach the coelomic epithelium lining the genital ridge, cellular contact causes the coelomic epithelia to differentiate into a primitive germinal epithelium. The germ cells become embedded in the primitive germinal epithelium during this process of differentiation. This combination of germinal epithelia and germ cells forms the sex cords. The connection of the sex cords to the coelomic wall (gonadal surface) is maintained at this point. The gonads are now histologically distinct, bipotent organs that may become testes or ovaries (Fig. 5.2). Inappropriate or incomplete developmental signals during this stage can result in the rare condition of hermaphroditism. True hermaphrodites have both ovaries and testes and are extremely rare in humans.
In a genetic male, gene products directed by activation of the SRY locus on the Y chromosome now cause the undifferentiated sex cords to enlarge, split and begin to form the primitive testis. Subepithelial mesenchyme arises between the germinal epithelium and the sex cords and cuts the cords off from the gonadal surface. The sex cords are now housed within the inner portion of the gonad – the testicular medulla. The primordial germ cells within the sex cords begin to differentiate into immature sperm cells called spermatogonia. The supporting sex cord cells form precursor Sertoli cells.
Ovarian differentiation occurs about 2 weeks later than testicular development. Initially, the sex cords of the developing ovary continue to proliferate while maintaining their connection with the gonadal surface. The germ cells begin to differentiate into primordial oocytes called oogonia within follicles. The epithelium surrounding the oogonia differentiates into granulosa cells. Subepithelial mesenchyme then invades the gonad and breaks up the sex cords, isolating the follicles. This mesenchyme will become the ovarian stroma. Unlike the testis, developing ovarian gametes are now housed in the outer portion of the gonad–the ovarian cortex.
The ovary and testes can be histologically distinguished from each other by the 8th embryonic (10th menstrual) week of pregnancy. The progeny of the germinal epithelium are now apparent as Sertoli cells in the male and granulosa cells in the female. Similarities between males and females in the endocrine function of these cells stem from their common ancestry. The mesenchyme arising beneath the germinal epithelium in the testis is the anlagen of testicular interstitial cells, also known as Leydig cells. The mesenchyme arising beneath the germinal epithelium of the ovary is the anlagen of ovarian stroma or thecal cells. Functional similarities in these two cell types will also be seen in the mature glands.
Once the undifferentiated gonads begin to develop into either ovaries or testes, the remainder of sexual differentiation is dependent on secretory products of the testes only. In the absence of these specific testicular secretions, the phenotype that develops is completely female. The ovary and its secretory products do not contribute to the development of the uterus, fallopian tubes, vagina or vulva.