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bryonic life with the development of male or female gonads. Therefore, at the time of fertilization, chromosomal sex or genetic sex is determined. Sexual differentiation is controlled by gonadal hormones that act at critical times during organogenesis. Testicular hormones induce mas-culinization, whereas feminization does not require (female) hormonal intervention. The process of sexual development is incomplete at birth, the secondary sex characteristics and a functional reproductive system are not fully developed until puberty.
Human somatic cells have 44 autosomes and 2 sex chromosomes. The female is homogametic (having two X chromosomes) and produces similar X-bearing ova. The male is heterogametic (having one X and one Y chromosome) and generates two populations of spermatozoa, one with X chromosomes and the other with Y chromosomes. The X chromosome is large, containing 80 to 90 genes responsible for many vital functions. The Y chromosome is much smaller, carrying only few genes responsible for testicular development and normal spermatogenesis. Gene mutation of genes on an X chromosome results in the transmission of X-linked traits, such as hemophilia and color-blindness, to male offspring, which, unlike females, cannot compensate with an unaffected allele.
Theoretically, by having two X chromosomes, the female has an advantage over the male, who has only one. However, because one of the X chromosomes is inactivated at the morula stage, the advantage is lost. Each cell randomly inactivates either the paternally or the maternally derived X chromosome, and this continues throughout the cell's progeny. The inactivated X chromosome is recognized cytologically as the sex chromatin or Barr body. In males, with more than one X chromosome, or in females, with more than two extra X chromosomes are inactivated and only one remains functional. This does not apply to the germ cells. The single active X chromosome of the sper-matogonium becomes inactivated during meiosis, and a functional X chromosome is not necessary for the formation of fertile sperm. The oogonium, however, reactivates its second X chromosome, and both are functional in oocytes and important for normal oocyte development.
Testicular differentiation requires a Y chromosome and occurs even in the presence of two or more X chromosomes. Gonadal sex determination is regulated by a testis-determining gene designated SRY (sex-determining region, Y chromosome). Located on the short arm of the Y chromosome, SRY encodes a DNA-binding protein, which binds to the target DNA in a sequence-specific manner. The presence or absence of SRY in the genome determines whether male or female gonadal differentiation takes place. Thus, in normal XX (female) fetuses, which lack a Y chromosome, ovaries, rather than testes, develop.
Whether possessing the XX or the XY karyotype, every embryo goes initially through an ambisexual stage and has the potential to acquire either masculine or feminine characteristics. A 4- to 6-week-old human embryo possesses indifferent gonads, and undifferentiated pituitary, hypothalamus, and higher brain centers.
The indifferent gonad consists of a genital ridge, derived from coelomic epithelium and underlying mes-enchyme, and primordial germ cells, which migrate from the yolk sac to the genital ridges. Depending on genetic programming, the inner medullary tissue will become the testicular components, and the outer cortical tissue will develop into an ovary. The primordial germ cells will become oogonia or spermatogonia. In an XY fetus, the testes differentiate first. Between weeks 6 and 8 of gestation, the cortex regresses, the medulla enlarges, and the seminiferous tubules become distinguishable. Sertoli cells line the basement membrane of the tubules, and Leydig cells undergo rapid proliferation. Development of the ovary begins at weeks 9 to 10. Primordial follicles, composed of oocytes surrounded by a single layer of granulosa cells, are discernible in the cortex between weeks 11 and 12 and reach maximal development by weeks 20 to 25.
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