Susceptibility of glycolytic enzyme activity and motility of spermatozoa from rat, mouse, and human to inhibition by proven and putative chlorinated antifertility compounds in vitro

Nonhormonal contraceptives that act by blocking energy metabolism within sp erm have the advantage over spermatogenic inhibitors by their fast onset of infertility and their almost immediate restoration of fertility after with drawal of the contraceptive agent. This study was done to test new chlorina ted compounds for their contraceptive potency on rodent and human sperm in vitro. Cells were incubated in a medium containing glucose as the sole ener gy source with 1-chloro-3-hydroxypropanone (CHOP) and 1,6-dichloro-1,6-dide oxy-D-fructose (DGDF), chlorinated analogues of glycolytic substrates, as w ell as racemic (R,S)-alpha -chlorohydrin (ACH). After incubation, enzymatic activity and kinematic parameters were estimated. A dose-dependent inhibit ion of the glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAP DH), of rat and mouse distal cauda epididymidal and human ejaculated sperm by AGH, CHOP, and DCDF was demonstrated. Triosephosphate isomerase (TPI) wa s inhibited by AGH, but not by CHOP and DCDF, irrespective of species. All compounds inhibited sperm motility and kinematic parameters with increasing concentration. The results confirm that inhibition of glycolytic enzymes o f sperm, including those of human, can be effectively brought about by a va riety of chloro-compounds that can be converted to (s)-3-chlorolactaldehyde , the stereospecific chloro-derivative of the enzyme's natural substrate, ( R)-glyceraldehyde 3-phosphate, and could be developed into contraceptive ag ents for men.