Review of Medical Physiology - William F. Ganong 2002

Endocrine System, Metabolism, and Reproduction
Gonads: Development and Function of the Reproductive System
Sex Differentiation and Development - Chromosomal Sex

Sex Chromosomes

At the genetic level, biological sex is determined by a pair of chromosomes known as sex chromosomes, as distinct from somatic chromosomes (autosomes). In humans and many mammals, these are the X and Y chromosomes. The presence of the Y chromosome is both necessary and sufficient for Testis determination; the product of the Gene responsible for this development is called SRY (sex-determining region of the Y chromosome). SRY is a DNA-binding regulatory protein that bends DNA and acts as a METABOLISM/31.html">Transcription factor for a cascade of genes required for testicular differentiation, including the gene for MIS (see below). The SRY gene is localized near the tip of the short arm of the human Y chromosome. Male Cells with a diploid chromosome Complement contain one X and one Y chromosome (XY karyotype), whereas female cells contain two X chromosomes (XX karyotype). During gametogenesis, Meiosis ensures that each normal mature oocyte receives a single X chromosome, whereas half of all normal spermatozoa carry an X chromosome and the other half carry a Y chromosome (Fig. 23-1). If an oocyte is fertilized by a Y-bearing spermatozoon, the resulting zygote has an XY complement and develops as a genetic male. When Fertilization is accomplished by an X-bearing spermatozoon, an XX complement is formed, resulting in a genetic female. Cell Division and the Chemical Nature of chromosomes are discussed in Chapter 1.

Human chromosomes

Human chromosomes can be examined in detail. When human cells are cultured in vitro, mitosis can be arrested in metaphase using colchicine. Exposure to a hypotonic solution causes the chromosomes to swell and disperse, enabling the preparation of cytological slides. Fluorescence and other staining techniques facilitate the identification and detailed analysis of individual chromosomes (Fig. 23-2). The normal complement consists of 46 chromosomes: in males, 22 pairs of autosomes plus an X and a Y chromosome; in females, 22 pairs of autosomes and two X chromosomes. Typically, individual chromosomes are arranged randomly in a karyotype. The individual pairs of autosomes are numbered 1 through 22 based on their morphological characteristics. Notably, the human Y chromosome is smaller than the X chromosome, which led to the hypothesis that Y-bearing spermatozoa are lighter, allowing them to swim faster through the female reproductive tract and reach the oocyte first. This hypothesis is supported by the fact that the number of newborn boys slightly exceeds that of girls.

Sex Chromatin

Following cell division, which begins during embryonic development, one of the two X chromosomes in the somatic cells of healthy females becomes inactivated. In pathological cases involving individuals with more than two X chromosomes, only one remains active. The normal process responsible for this inactivation is initiated at the X-inactivation center of the chromosome. Inactivation is mediated by the Xist gene, which produces a non-coding mRNA that drives the process. However, the exact MOLECULAR MECHANISMS OF inactivation are not yet fully understood. The choice of which chromosome becomes active appears to be random. Consequently, in normally developing females, approximately half of the cells have an active maternal X chromosome, while the other half have an active paternal X chromosome. Selection also occurs during subsequent cell divisions, resulting in some somatic cells of a healthy female containing the paternally derived active X chromosome, while others contain the maternally inherited active X chromosome.

In normal cells, the inactive X chromosome condenses and can be visualized in various cell types, typically adjacent to the nuclear membrane, as a Barr body (Fig. 23-3). Thus, the number of Barr bodies in a cell corresponds to the number of X chromosomes minus one. The inactive X chromosome appears as a small drumstick-like appendage of chromatin protruding from The Nucleus in 1% to 15% of polymorphonuclear leukocytes in females, and is absent in males (see Fig. 23-3). The Barr body is also referred to as sex chromatin.