Loss of mammalian glutaminase orthologs impairs sperm function in Caenorhabditis elegans.

Abstract

The decline in sperm function is a major cause of human male infertility. Glutaminase, a mitochondrial enzyme that catalyzes the hydrolysis of glutamine to generate glutamate, takes part in many diverse biological processes such as neurotransmission, metabolism, and cellular senescence. Here we report the role of glutaminase in regulating sperm function. By generating a triple mutant that harbors a loss-of-function allele for each of all three mammalian glutaminase orthologs, we found that glutaminase gene activity is required for optimal Caenorhabditis elegans sperm function. Tissue-specific gene manipulations showed that germline glutaminase activity plays an important role. Moreover, transcriptional profiling and antioxidant treatment suggested that glutaminase promotes sperm function by maintaining cellular redox homeostasis. As maintaining a low level of ROS is crucial to human sperm function, it is very likely that glutaminase plays a similar role in humans and therefore can be a potential target for treating human male infertility.