Spermatid head retention as a marker of 2,5-hexanedione-induced testicular toxicity in the rat.

Histopathological analysis is a basic methodology for assessing testicular injury after exposure to candidate therapeutics or toxicants. One possible injury response in rat testis is the failure of step 19 spermatids to spermiate. Such spermatids are transported toward the basement membrane, where they are retained for degradation by Sertoli cells. In control rats, these retained spermatid heads (RSH) were observed at Stages IX-XII. Exposure to the Sertoli cell toxicant, 2,5-hexanedione (HD), for eighteen days at 0.08%-1.0% in drinking water resulted in a dose-dependent increase in the number of RSH at Stages IX-XII (no observed effect level [NOEL], 0.14%). To explore the dynamics of spermatid head retention, rats were treated with 0.33% or 1% HD for various durations and RSH were assessed across all stages. After 0.33% HD exposure for eighteen days, there were more RSH present in Stage IX-XII tubules compared to control. Numbers of RSH dropped back to control levels after four weeks of recovery after the eighteen-day exposure. Exposure of rats to 1% HD for eighteen days resulted in markedly elevated numbers of RSH at Stages IX-II/III. There was no evidence of other histopathological alterations. These data identify RSH as a sensitive histopathological marker of testicular toxicity for subacute HD exposure.