alpha-chlorohydrin inhibits glyceraldehyde-3-phosphate dehydrogenase in multiple organs as well as in sperm

Numerous studies have documented inhibitory effects of alpha -chlorohydrin (ACH) on glyceraldehyde-3-phosphate dehydrogenase (G3PDH) activity in sperm atozoa. A sperm-specific G3PDH isoform has been described. The possibility that AGH may inhibit G3PDH in cell types other than sperm was investigated in this work. In addition, the onset of AGH-induced epididymal toxicity was described. Changes to epididymal histology occurred 6 h following a single dose of ACH (50 mg/kg po) and were confined to the proximal initial segmen t. By 24 h, no epithelial cells lined the basement membrane of that region. Three h after ACH administration (50 mg/kg po), G3PDH activity was signifi cantly decreased in sperm (85%) as well as in kidney (31%), liver (49%), an d epididymis (35%). Enzyme activity remained inhibited at 6 and 24 h, G3PDH was immunolocalized in the epididymis and staining was highest in the effe rent ducts and initial segment as well as in smooth muscle. Since G3PDH is a microtubule-associated protein and microtubule-dependent endocytosis occu rs in the epididymis, beta -tubulin was also immunolocalized. beta -tubulin densely stained the apical region of initial segment and caput epithelial cells. Disruption of beta -tubulin immunostaining correlated with the local ization and onset of the lesion. Co-localization of G3PDH and beta -tubulin immunostaining was not observed although both antibodies most densely stai ned the initial segment. Our data indicate that histologic changes to the p roximal initial segment of the epididymis occur rapidly, but subsequent to G3PDH inhibition. Moreover, ACH inhibition of G3PDH is not confined to sper m, although the sperm enzyme is most sensitive to inhibition.