Sexual Development and Disorders of sex development (DSD)

Abstract

Genetic sex is determined at the time of conception. In humans, the sexual phenotype is established in three steps (1) The sex chromosome complement of the embryo, (2) Gonadal differentiation, and (3) Differentiation of the internal duct and the external genitalia as female or male occurs as a response to hormones produced by the differentiated gonads. A number of genes, i.e., SRY, SOX9, SF1, DAX1, WT1, have been shown to influence these early and late sexual develop-ment processes. Mammalian gonads arise from the bilateral genital ridges and have the potential to develop into testes or ovaries. The Y chromosome (46, XY) is key to the differentiation of germ cells into testes. In the absence of a Y chromo-some and the presence of a second X chromosome (46, XX) or in the absence of a gonad, development will be female in nature. The primary testis determinant is the SRY (Sex determining Region Y) gene, which is located on the short arm of the Y chromosome, and initiates the testicular differentiation from the Wolffian duct. Hormones produced from the testis (Müllerian inhibiting substance (MIS, MIF: Müllerian inhibiting factor, AMH: anti Müllerian hormone), secreted from the Sertoli cells, and testosterone, secreted from the Lydig cells steer the further development of the remainder of the genital tract. MIS mediates the regression of the Müllerian ducts (paramesonephric duct), whereas the androgens main-tain the Wolffian ducts. In the absence of MIS, the internal ducts differentiate into fallopian tubes, the uterus, and the upper vagina from the Müllerian ducts. Unlike the internal genitalia, the external genitalia are neutral primordially, and can differentiate into either male or female structures depending on the gonadal steroid hormone signals. Gonadal differ-entiation involves a complex interplay of developmental pathways. Normal sexual differentiation will be considered in order to provide a basis for understanding the various types of abnormal development. This issue will present disorders of sexual development (DSD) as abnormal sexual development based on normal sexual development. (J. Nihon Univ. Med. Ass., 2013; 72 (3): 129–136) Sex gender iden-tity disorder (GID) intersex (IS) sexual minority () (Gender-based Biology) 1) (sex) 2) (gender identity)3) (sexual orientation) 3 (chromosomal sex) (gonadal sex) (sexual phenotype) 3 (DSD: Disorders of sex development) Turner Klinefelter (AIS: androgen insensitivity syn-drome) (CAH: congenital adrenal hyperplasia)