This chapter discusses the known disorders of ovarian failure and ovarian resistance and the related genes. Ovarian failure and ovarian resistance in humans have a variety of causes. Failure may be complete or premature, occurring earlier (younger than 35 or 40 years) than the expected age of menopause. Either complete or premature ovarian failure has long been deduced to result from either deletions of the X chromosome or Mendelian causes; however, only rarely is the actual gene known. Primordial germ cells originate in the endoderm of the yolk sac and migrate to the genital ridge to form the indifferent gonad with 46,XY and 46,XX gonads being initially indistinguishable. Indifferent gonads develop into testes if the embryo, or more specifically the gonadal stroma, is 46,XY. Testes become morphologically identifiable 7 to 8 weeks following conception (9 to 10 weeks gestational or menstrual weeks). Ovaries become identifiable thereafter. In the absence of a Y chromosome, the indifferent gonad develops into an ovary. Transformation into fetal ovaries begins at 50 and 55 days of embryonic development. It is debatable whether female (ovarian) differentiation is truly a default (constitutive) pathway, or whether a specific gene product directs primary ovarian differentiation.
