8,10 Interestingly, Top3b and TDRD3 mutations have also been linked to germ cell dysfunction, including age at natural menopause.32–35 Moreover, TDRD3 variants are associated with premature menopause36 and polycystic ovary syndrome.37 Furthermore, human individuals and mice carrying Top3b mutations show defective spermatogenesis and infertility.38,39 These data indicate that Top3b-TDRD3 may function critically in germ cells in mammals. This evidence concerns the gene TDRD3 and polycystic ovary syndrome.