Fate of germ cells in 2,5-hexanedione-induced testicular injury. II. Atrophy persists due to a reduced stem cell mass and ongoing apoptosis.
The Sertoli cell toxicant 2,5-hexanedione (2,5-HD) causes irreversible testicular atrophy in rats. After toxicant exposure, only Sertoli cells, stem cells, and a few spermatogonia remain in the seminiferous epithelium. In this study, the number, type, and fate of the remaining germ cells were determined. Male Sprague-Dawley rats were exposed to 1% 2,5-HD in drinking water for 5 weeks and then sacrificed 12 or 40 weeks after the start of exposure. Cell counts determined that the stem cell population was diminished in size, but made up a significant portion of the remaining germ cells. The remaining germ cells were primarily type A spermatogonia. Modeling of spermatogonial divisions suggested that most spermatogonia undergo degeneration at the level of type A3 spermatogonia after 2,5-HD-induced atrophy. Apoptosis was demonstrated to occur in the remaining germ cells by nuclear morphology and in situ analysis of DNA fragmentation. Quantitation indicated that apoptosis occurred in a majority of stem cell progeny. We conclude that the irreversibility of 2,5-HD-induced testicular injury results from the reduced size of the stem cell population as well as a block in germ cell development at the level of type A spermatogonia.
Allard
E K
EK
Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA.
Boekelheide
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001284:Atrophy / Q000139:chemically induced; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004247:DNA / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D006588:Hexanones / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013093:Spermatogonia / Q000187:drug effects* / Q000473:pathology; D013194:Staining and Labeling / Q000379:methods; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology*
D002800:Cholinesterase Inhibitors; D006588:Hexanones; D004247:DNA; C011269:2,5-hexanedione