Group III secreted phospholipase A2 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 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.
Sato
Hiroyasu
H
Biomembrane Signaling Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Taketomi
Yoshitaka
Y
Isogai
Yuki
Y
Miki
Yoshimi
Y
Yamamoto
Kei
K
Masuda
Seiko
S
Hosono
Tomohiko
T
Arata
Satoru
S
Ishikawa
Yukio
Y
Ishii
Toshiharu
T
Kobayashi
Tetsuyuki
T
Nakanishi
Hiroki
H
Ikeda
Kazutaka
K
Taguchi
Ryo
R
Hara
Shuntaro
S
Kudo
Ichiro
I
Murakami
Makoto
M
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
D010713:Phosphatidylcholines; D054520:Group III Phospholipases A2