Modern genetics and experimental embryology make it clear that, in most species of mammals, the multiple differences between the male and the female depend primarily on a single chromosome (the Y chromosome) and a single pair of endocrine structures, the testes in the male and the ovaries in the female. The differentiation of the primitive gonads into testes or ovaries in utero is genetically determined in humans, but the formation of male genitalia depends on the presence of a functional, secreting testis; in the absence of testicular tissue, development is female.
Sex is determined genetically by two chromosomes, called the sex chromosomes, to distinguish them from the somatic chromosomes (autosomes). In humans and many other mammals, the sex chromosomes are called X and Y chromosomes. The Y chromosome is necessary and sufficient for the production of testes, and the testis-determining gene product is called SRY (for sex-determining region of the Y chromosome). SRY is a DNA binding regulatory protein. It bends the DNA and acts as a transcription factor that initiates transcription of a cascade of genes necessary for testicular differentiation, including the gene for mullein inhibiting substance (MIS; see below). The gene for SRY is located near the tip of the short arm of the human Y chromosome. Male cells with the diploid number of chromosomes contain an X and a Y chromosome (XY pattern), whereas female cells contain two X chromosomes (XX pattern).
Human chromosomes can be studied in detail. Human cells are grown in tissue culture; treated with the drug colchicine, which arrests mitosis at the metaphase; exposed to a hypotonic solution that makes the chromosomes swell and disperse; and then “squashed” onto slides. Staining techniques make it possible to identify the individual chromosomes and study them in detail. There are 46 chromosomes: in males, 22 pairs of autosomes plus an X chromosome and a Y chromosome; in females, 22 pairs of autosomes plus two X chromosomes. The individual chromosomes are usually arranged in an arbitrary pattern (karyotype).
Soon after cell division has started during embryonic development, one of the two X chromosomes of the somatic cells in normal females becomes functionally inactive. In abnormal individuals with more than two X chromosomes, only one remains active. The process that is normally responsible for inactivation is initiated in an X-inactivation center in the chromosome, probably via the Trans activating factor CTCF (for CCCTC-binding factor), which is also induced in gene imprinting. However, the details of the inactivation process are still incompletely understood. The choice of which X chromosome remains active is random, so normally one X chromosome remains active in approximately half of the cells and the other X chromosome is active in the other half. The selection persists through subsequent divisions of these cells, and consequently, some of the somatic cells in adult females contain an active X chromosome of paternal origin and some contain an active X chromosome of maternal origin.
Development of the Gonads
On each side of the embryo, a primitive gonad arises from the genital ridge, a condensation of tissue near the adrenal gland. The gonad develops a cortex and a medulla. Until the sixth week of development, these structures are identical in both sexes. In genetic males, the medulla develops during the seventh and eighth weeks into a testis, and the cortex regresses.
Aberrant sexual differentiation
From the preceding discussion, it might be expected that abnormalities of sexual development could be caused by genetic or hormonal abnormalities as well as by other nonspecific teratogenicity influences, and this is indeed the case. The major classes of abnormalities. Nondisjunction of sex chromosomes during the first division in meiosis results in distinct defects. Meiosis is a two-stage process, and although nondisjunction usually occurs during the first meiotic division, it can occur in the second, producing more complex chromosomal abnormalities. In addition, nondisjunction or simple loss of a sex chromosome can occur during the early mitotic divisions after fertilization. The result of faulty mitoses in the early zygote is the production of mosaics, in which two or more populations of cells have different chromosome complements. True hermaphroditism, the condition in which the individual has both ovaries and testes, is probably due to XX/XY mosaics and related mosaic patterns, although other genetic aberrations are possible.
Differences between males and females depend primarily on a single chromosome (the Y chromosome) and a single pair of endocrine structures (the gonads); testes in the male and ovaries in the female.
The gonads have a dual function: the production of germ cells (gametogenesis) and the secretion of sex hormones. The testes secrete large amounts of androgens, principally testosterone, but they also secrete small amounts of estrogens. The ovaries secrete large amounts of estrogens and small amounts of androgens.