Intracytoplasmic sperm; injection (ICSI) has been used in combination:with
testicular sperm extraction to achieve pregnancies in couples:with severe m
ale-factor infertility, yet many of the underlying genetic mechanisms remai
n largely unknown. To investigate nondisjunction in mitotic and meiotic ger
m cells, we performed three-color FISH to detect numeric chromosome aberrat
ions in testicular tissue samples from infertile men confirmed to have impa
ired spermatogenesis of unknown cause. FISH was employed to determine the r
ate of sex-chromosome aneuploidy in germ cells. Nuclei were distinguished a
s haploid or diploid, respectively. The overall incidence of sex-chromosome
aneuploidy in germ cells was found to be significantly higher (P <.00001)
in all three abnormal histopathologic patterns (range 39.0%-43.5%) as compa
red with normal controls (29.1%). The relative ratio of normal to aneuploid
nuclei in the diploid cells of patients with impaired spermatogenesis was
similar to 1.0, a >300% decrease when compared with the 4.42 ratio detected
in patients with normal spermatogenesis. These results provide direct evid
ence of an increased incidence of sex-chromosome aneuploidy observed in ger
m cells of men with severely impaired spermatogenesis who might be candidat
es:for ICSI with sperm obtained directly from the testis. The incidence of
aneuploidy was significantly greater among the diploid nuclei, which sugges
ts that chromosome instability is a result of altered genetic control durin
g mitotic cell division and proliferation during spermatogenesis.