Germ cell loss in the XXY male mouse: Altered X-chromosome dosage affects prenatal development

Abstract

Male mammals with two X chromosomes are sterile due to the demise of virtually all germ cells; however, the underlying reasons for the germ cell loss remain unclear. The use of a breeding scheme for the production of XXY male mice has allowed us to experimentally address the question of when and why germ cells die in the XXY testis and whether the defect is due to the presence of an additional X chromosome in the soma, the germ cells themselves, or both. Our studies demonstrate that altered X‐chromosome dosage acts to impair germ cell development in the testis at a much earlier stage than suggested by previous studies of XX sex‐reversed males or XX/XY chimeras. Specifically, we noted significantly reduced germ cell numbers in the XXY testis during the period of germ cell proliferation in the early stages of testis differentiation. Although the somatic development of the XXY testis is morphologically and temporally normal, our studies indicate that germ cell demise reflects a defect in somatic/germ cell communication, since, in an in vitro system, the proliferative potential of fetal germ cells from XXY males is indistinguishable from that of normal males. Mol. Reprod. Dev. 49:101–111, 1998. © 1998 Wiley‐Liss, Inc.

Transradial coronary brachytherapy with the Novoste beta‐rail system

“…Surprisingly, germ cell loss seems to be an ongoing process occurring from the moment when female germ cells enter meiosis (56 dpc) until birth. Similar results have been described in both XX Sxr and XXY mouse testes, where germ cell number significantly decreased in the early stages of testis differentiation and was absent after birth (McLaren, 1981, 1983; Hunt et al, 1998). It seems that germ cell loss could principally be due to an altered X‐chromosome dosage.…”

Transient development of ovotestes in XX Sox9 transgenic mice

“…This has not be described in XY ovotestes (Eicher and Washburn, 2001) suggesting that the antagonism between β-catenin and continual expression of Sox9 cause somatic cells to undergo apoptosis. Although we did not detect germ cell apoptosis at E14.5 in transgenic ovotestes, it has been shown that germ cell undergo degeneration at birth in XXY testis (Hunt et al, 1998). This suggests that degeneration could also occurs in XX Wt1:Sox9 Tg/ + testes.…”

Gonadal Effects of a Mouse Denys-Drash Syndrome Mutation

“…Adult Leydig cells were present in both control XXY and DDS testes. The germ cell aplasia in adult control XXY testes is consistent with reports that germ cell loss in these mice initiates during late foetal/early neonatal development (Hunt et al, 1998;Lue et al, 2001).…”