Group III secreted phospholipase [A.sub.2] regulates epididymal sperm maturation and fertility in mice

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.sup.2] ([sPLA.sup.2]-III), a member of...

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Bibliographic Details
Published in:The Journal of clinical investigation 2010-05, Vol.120 (5)
Main Authors: Sato, Hiroyasu, Taketomi, Yoshitaka, Isogai, Yuki, Miki, Yoshimi, Yamamoto, Kei, Masuda, Seiko, Hosono, Tomohiko, Arata, Satoru, Ishikawa, Yukio, Ishii, Toshiharu, Kobayashi, Tetsuyuki, Nakanishi, Hiroki, Ikeda, Kazutaka, Taguchi, Ryo, Hara, Shuntaro, Kudo, Ichiro, Murakami, Makoto
Format: Article
Language:English
Subjects:
Fertility
Growth
Health aspects
Phospholipases
Physiological aspects
Spermatozoa
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Summary: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.sup.2] ([sPLA.sup.2]-III), a member of the secreted phospholipase [A.sup.2] ([sPLA.sup.2]) family, is expressed in the mouse proximal epididymal 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.sup.[-/-]] 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 epididymal spermatozoa in [PlA2g3.sup.[-/-]] mice had both flagella with abnormal axonemes and aberrant acrosomal structures. During epididymal transit, phosphatidylcholine in the membrane of [PlA2g3.sup.[+/+]] sperm underwent a dramatic shift in its acyl groups from oleic, linoleic, and arachidonic acids to docosap-entaenoic and docosahexaenoic acids, whereas this membrane lipid remodeling event was compromised in sperm from [PlA2g3.sup.[-/-]] mice. Moreover, the gonads of [PlA2g3.sup.[-/-]] mice contained less 12/15-lipoxygenase metabolites than did those of [PlA2g3.sup.[+/+]] mice. Together, our results reveal a role for the atypical [sPLA.sup.2] family member [sPLA.sup.2]-III in epididymal lipid homeostasis and indicate that its perturbation may lead to sperm dysfunction.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI40493