Sex Begins in the Womb - Exploring the Biological Contributions to Human Health - NCBI Bookshelf

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Institute of Medicine (US) Committee on Understanding the Biology of Sex and Gender Differences; Wizemann TM, Pardue ML, editors. Exploring the Biological Contributions to Human Health: Does Sex Matter? Washington (DC): National Academies Press (US); 2001.

Sex differences of importance to health and human disease occur throughout the life span, although the specific expression of these differences varies at different stages of life. Some differences originate in events occurring in the intrauterine environment, where developmental processes differentially organize tissues for later activation in the male or female. In the prenatal period, sex determination and differentiation occur in a series of sequential processes governed by genetic and environmental factors. During the pubertal period, behavioral and hormonal changes manifest the secondary sexual characteristics that reinforce the sexual identity of the individual through adolescence and into adulthood. Hormonal events occurring in puberty lay a framework for biological differences that persist through life and that contribute to variable onset and progression of disease in males and females. It is important to study sex differences at all stages of the life cycle, relying on animal models of disease and including sex as a variable in basic and clinical research designs.

All human individuals—whether they have an XX, an XY, or an atypical sex chromosome combination—begin development from the same starting point. During early development the gonads of the fetus remain undifferentiated; that is, all fetal genitalia are the same and are phenotypically female. After approximately 6 to 7 weeks of gestation, however, the expression of a gene on the Y chromosome induces changes that result in the development of the testes. Thus, this gene is singularly important in inducing testis development. The production of testosterone at about 9 weeks of gestation results in the development of the reproductive tract and the masculinization (the normal development of male sex characteristics) of the brain and genitalia. In contrast to the role of the fetal testis in differentiation of a male genital tract and external genitalia in utero, fetal ovarian secretions are not required for female sex differentiation. As these details point out, the basic differences between the sexes begin in the womb, and this chapter examines how sex differences develop and change across the lifetime. The committee examined both normal and abnormal routes of development that lead individuals to become males and females and the changes during childhood, reproductive adulthood, and the later stages of life.

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