Normal male sexual differentiation and aetiology of disorders of sex development

Abstract

Fetal sex development consists of three sequential stages: a) the undifferentiated stage, when identical primitive structures develop in the XY and XX embryos, b) gonadal differentiation into testes or ovaries, and c) the differentiation of internal and external genitalia, which depends on the action of testicular hormones. Disorders of sex development (DSD) may result from defects in any of these stages. Abnormal formation of the anlagen of internal and/or external genitalia in early embryonic development results in Malformative DSD. In patients with a Y chromosome, defects in testis differentiation drive to early-onset fetal hypogonadism affecting whole testicular function, a condition named Dysgenetic DSD. In Non-dysgenetic DSD, the underlying pathogenesis may involve early-onset fetal hypogonadism affecting specifically either Leydig or Sertoli cell function, or male hormone end-organ defects in patients devoid of fetal hypogonadism. Understanding the pathogenesis is useful for an efficient early diagnosis approach, which is necessary for adequate decision making in the management of DSD.