Germ cell loss in the XXY male mouse: altered X-chromosome dosage affects prenatal development.
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.
Hunt
P A
PA
Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4955, USA.
Worthman
C
C
Levinson
H
H
Stallings
J
J
LeMaire
R
R
Mroz
K
K
Park
C
C
Handel
M A
MA
D000818:Animals; D000831:Animals, Newborn; D001947:Breeding; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D004195:Disease Models, Animal; D018628:Gene Dosage; D005854:Germ Cells / Q000473:pathology*; D007985:Leydig Cells / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014960:X Chromosome / Q000235:genetics / Q000473:pathology*