In addition to male or ambiguous external genitalia and hypogenitalism, gonadal biopsies revealed the presence of testicular structures and ovotesticular morphology (strictly 46,XX ovotesticular DSD) in affected XX individuals.134,135 These data establish RSPO1 as a human ovary-determining gene with antitestis functions, in line with the ‘Z’ hypothesis discussed above. Here, RSPO1 is linked to disorder of sexual differentiation.