Sexual Differentiation or Gender Differentiation

Afza.Malik GDA

Gender Differentiation and its Abnormalities

Sexual Differentiation  or Gender Differentiation

 Sexual Differentiation  or Gender Differentiation Embryo sex, Genetic sex Abnormal Development Chromosome Abnormalities

    The means by which the embryo differentiates is controlled by the sex chromosomes. This is known as genetic sex. The normal chromosome complement is 46, including 22 autosomes derived from each parent. An embryo that contains 45 chromosomes and has the sex chromosomes XY will develop as a male. 

    If the sex chromosomes are XX, the embryo will differentiate into a female. The resulting development of the gonad will create either a testis or an ovary. This is known as gonadal sex. Subsequent development of the internal and external genitalia gives phenotypic sex or the sex of appearance. Cerebral differentiation to a male or female orientation is known as brain sex.

Genetic Sex

    In the developing embryo with a genetic complement of 46 XY, it is the presence of the Y chromosome that determines that the undifferentiated gonad will become a testis. Absence of the Y chromosome will result in the development of an ovary. 

    On the short arm of the Y chromosome is a region known as the SRY gene, which is responsible for the determination of testicular development as it produces a protein known as testicular determining factor (TDF). TDF directly influences the undifferentiated gonad to become a testis. When this process occurs, the testis also produces Müllerian inhibitor.

    The undifferentiated embryo contains both Wolffian and Müllerian ducts. The Wolffian ducts have the potential to develop into the internal organs of the male, and the Mullerian ducts into the internal organs of the female. If the testis produces Müllerian inhibitor, the Mullerian ducts regress.

    The testis differentiates into two cell types, Leydig cells and Sertoli cells. The Sertoli cells are responsible for the production of Mullerian inhibitor, which leads to Mullerian regression. The Leydig cells produce testosterone, which promotes the development of the Wolffian duct, leading to the development of was deferens, the epididymis and the seminal vesicles. 

    Testosterone by itself does not have a different effect on the cloaca; In order to exert its androgenic effects, it needs to be converted by the cloacal cells through the enzyme 5u-reductase to dihydrotestosterone. These androgenic effects lead to the development of the penis and the scrotum,

    The absence of Y chromosome and the presence of two X chromosomes mean that Müllerian inhibitor is not created, and the Müllerian ducts persist in the female. The absence of testosterone means that the Wolffian ducts regress, and the failure of androgen to affect the cloaca leads to an external female phenotype.

Abnormal Development

    Any aberration in development that results in an unexpected developmental sequence of events may be mediated in a number of ways.

Chromosome Abnormalities

    In an embryo that loses one of its sex chromosomes, the total complement of chromosomes will be reduced to 45, leaving a viable fetus only where this is 45 XO (Turner's syndrome). Here, the absence of the second X chromosome or Y chromosome means there is no testicular development and therefore the phenotype is female. 

    The gonad is, however, unable to complete its development and, although it initially differentiates to be an ovary, the oogonia are unable to complete their development and at birth only the stroma of the ovary is present (streak ovaries). Thus, in Turner's syndrome, the absence of a functional ovary means that there is no estrogen production at puberty, and secondary sexual characteristics cannot develop.

    As the genes involved in achieving final height are shared by the sex chromosomes, the absence of one sex chromosome will also lead to short stature. In females who have an XY karyotype, a mutation at the site on the short arm of the Y chromosome resulting in failure of production of TDF will mean there is no testicular development (XY gonadal agenesis). 

    The default phenotypic state is female. In these circumstances, the absence of a testis means that the internal genitalia will persist as a result of the development of Müllerian structures, and the Wolffian ducts will regress. The external genitalia will be female.

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