Chemical interference with sperm metabolic pathways.

Abstract

During the 1960s, the quest for a simple non-steroidal chemical possessing male antifertility activity culminated with the discovery of the activity of alpha-chlorohydrin in 1970. Investigations into the mechanism of action of this compound revealed that it was affecting the glycolytic pathway within mature spermatozoa through its conversion to an inhibitory metabolite. Use of these and other simple chemical inhibitors has subsequently led to a clearer understanding of the metabolic pathways involved in the generation of ATP, which is necessary for sperm motility. Mature boar spermatozoa from the cauda epididymidis are almost totally reliant on the glycolytic pathway, not necessarily for the immediate generation of ATP, but for the ultimate production of lactate, which appears to be the sole substrate used for the mitochondrial production of ATP. The only exogenous substrates that support lactate production in vitro are fructose, glucose, glycerol and glycerol 3-phosphate and when these substrates are plentiful, there is evidence that compounds can be retained as such or as intermediates of the glycolytic pathway. When exogenous substrates are limited, the cells have the capability to mobilize endogenous compounds and to maintain the continuous synthesis of ATP.