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.

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.