[摘要]：Although lipid metabolism is thought to be important for the proper maturation and function of spermatozoa, the molecular mechanisms that underlie this dynamic process in the gonads remains incompletely understood. Here, we show that group III phospholipase A(2) (sPLA(2)-III), a member of the secreted phospholipase A(2) (sPLA(2)) family, is expressed in the mouse proximal epidiciymal epithelium and that targeted disruption of the gene encoding this protein (Pla2g3) leads to defects in sperm maturation and fertility. Although testicular spermatogenesis in Pla2g3(-/-) mice was grossly normal, spermatozoa isolated from the cauda epididymidis displayed hypomotility, and their ability to fertilize intact eggs was markedly impaired. Transmission EM further revealed that epidiciymal spermatozoa in Pla2g3(-/-) mice had both flagella with abnormal axonemes and aberrant acrosomal structures. During epididymal transit, phosphatidylcholine in the membrane of Pla2g3(+/+) sperm underwent a dramatic shift in its acyl groups from oleic, linoleic, and arachidonic acids to docosapentaenoic and docosahexaenoic acids, whereas this membrane lipid remodeling event was compromised in sperm from Pla2g3(-/-) mice. Moreover, the gonads of Pla2g3(-/-) mice contained less 12/15-lipoxygenase metabolites than did those of Pla2g3(+/+) mice. Together, our results reveal a role for the atypical sPLA(2) family member sPLA(2)-III in epididymal lipid homeostasis and indicate that its perturbation may lead to sperm dysfunction.
