Role of retinoic acid in meiosis

To produce haploid gametes, mitotic germ cells in both sexes must transition to the specialized meiotic program. The molecular details underlying this transition - termed meiotic initiation - are poorly defined in higher eukaryotes, especially mammals. In mammals, the current mechanistic dogma is the signal, or 'meiosis inducing substance' (MIS), triggering germ cell meiotic initiation is provided by retinoic acid (RA). However, over the past twenty years a considerable number of reports using both genetic and pharmacologic approaches have been published that alternatively support or challenge RA's role as the mammalian MIS. Here, we attempt to fairly describe this conflicting evidence in the hopes that it will stimulate future conversations and design of studies to elucidate the molecular and cellular mechanisms driving meiotic initiation in the mammalian germline.