Germ cell development in the XXY mouse: Evidence that X chromosome reactivation is independent of sexual differentiation

Prior to entry into meiosis, XX germ cells in the fetal ovary undergo X chr omosome reactivation. The signal for reactivation is thought to emanate fro m the genital ridge, but it is unclear whether it is specific to the develo ping ovary. To determine whether the signals are present in the developing testis as well as the ovary, we examined the expression of X-linked genes i n germ cells from XXY male mice. To facilitate this analysis, we generated XXY and XX fetuses carrying X chromosomes that were differentially marked a nd subject to nonrandom inactivation. This pattern of nonrandom inactivatio n was maintained in somatic cells but, in XX as well as XXY fetuses, both p arental alleles were expressed in germ cell-enriched cell populations. Beca use testis differentiation is temporally and morphologically normal in the XXY testis and because all germ cells embark upon a male pathway of develop ment, these results provide compelling evidence that X chromosome reactivat ion in fetal germ cells is independent of the somatic events of sexual diff erentiation. Proper X chromosome dosage is essential for the normal fertili ty of male mammals, and abnormalities in germ cell development are apparent in the XXY testis within several days of X reactivation. Studies of except ional germ cells that survive in the postnatal XXY testis demonstrated that surviving germ cells are exclusively XY and result from rare nondisjunctio nal events that give rise to clones of XY cells. (C) 1999 Academic Press.