Germ-cell nondisjunction in testes biopsies of men with idiopathic infertility

Citation
Wj. Huang et al., Germ-cell nondisjunction in testes biopsies of men with idiopathic infertility, AM J HU GEN, 64(6), 1999, pp. 1638-1645
Citations number
45
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
Journal title
AMERICAN JOURNAL OF HUMAN GENETICS
ISSN journal
00029297 → ACNP
Volume
64
Issue
6
Year of publication
1999
Pages
1638 - 1645
Database
ISI
SICI code
0002-9297(199906)64:6<1638:GNITBO>2.0.ZU;2-Y
Abstract
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.