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.
