Cisplatin disrupts mammalian spermatogenesis, but does not affect recombination or chromosome segregation.
Meiotic recombination is initiated by a series of double-strand breaks (DSBs) in areas of the genome that generally contain promoters and feature an open chromatin configuration [T.D. Petes, Meiotic recombination hot spots and cold spots, Nat. Rev. Genet. 2 (2001) 360-369]. To investigate whether induced DSBs likewise lead to recombinational repair and whether the placement of new exchange events alters normal patterns of recombination, we used the chemotherapeutic drug cisplatin (CP) to generate additional DSBs throughout the mouse genome. Treatment with CP impaired spermatogenesis, as exhibited by reductions in sperm counts, reductions in both testicular size and weight, changes in the distribution of cells at various prophase I substages, prolonged increases in germ cell apoptosis, and an increased incidence of synaptic abnormalities. Unexpectedly, however, no obvious effect on genome-wide recombination levels in CP-treated animals was observed, nor was the level of aneuploidy increased in sperm from exposed males.
Cherry
Sheila M
SM
Department of Genetics and Center for Human Genetics, Case Western Reserve University, University Hospitals of Cleveland, OH 44106-4955, USA.
Hunt
Patricia A
PA
Hassold
Terry J
TJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020090:Chromosome Segregation / Q000187:drug effects*; D002875:Chromosomes / Q000235:genetics; D002945:Cisplatin / Q000633:toxicity*; D004249:DNA Damage; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects
D002945:Cisplatin