title: Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice.
abstract: 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 A2 (sPLA2-III), a member of the secreted phospholipase A2 (sPLA2) 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-/- 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-/- 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 sPLA2 family member sPLA2-III in epididymal lipid homeostasis and indicate that its perturbation may lead to sperm dysfunction.
authors.affiliation: Biomembrane Signaling Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sato
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Taketomi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Isogai
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Miki
authors.forename: Kei
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Seiko
authors.initials: S
authors.lastname: Masuda
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Hosono
authors.forename: Satoru
authors.initials: S
authors.lastname: Arata
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ishii
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kudo
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D004822:Epididymis / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D054520:Group III Phospholipases A2 / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D010713:Phosphatidylcholines / Q000378:metabolism; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D010713:Phosphatidylcholines; D054520:Group III Phospholipases A2