ABSTRACT
Until recently female sexual differentiation was thought to be occurring in the absence of a Y chromosome. However, it is well accepted now that ovarian development is induced by specific genes such as DAX1 located on the short arm of the X chromosome, which down-regulates the steroidogenesis factor 1 (SF1) activity. The growth factor signaling molecule (WNT4) participates in ovarian differentiation. 1 Its early presence in the gonadal ridge is up-regulated in females but not so in males. In the absence of müllerian inhibiting substance (MIS), the paramesonephric (müllerian) ducts are stimulated by estrogens to form the upper vagina, cervix, uterus, and uterine tubes. Likewise, the external genitalia in the indifferent stage are acted upon by estrogens to develop into the lower vagina, labia majora, labia minora, and clitoris. Another line of evidence indicates that ovaries play no role in primary sexual development, as testes are required for masculinity and repression of femininity. 2 In the indifferent stage of development the gonadal sex is not determinable and both mesonephric and paramesonephric duct systems are present. Thus up to the 17 mm crown-rump length stage (estimated age 46 days 3 ), the gonads cannot be identified externally either as ovaries or testes. However, genetically, the sex was already established as early as at the time of fertilization.
