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 A 2 (sPLA 2 -III), a member of the secreted phospholipase A 2 (sPLA 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 -/-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 sPLA 2 family member sPLA 2 -III in epididymal lipid homeostasis and indicate that its perturbation may lead to sperm dysfunction.

Structural Characteristics and Evolution of theProtobothrops elegansPancreatic Phospholipase A2Gene in Contrast with Those ofProtobothropsGenus Venom Phospholipase A2Genes

“…6,7) Group III PLA 2 s are found in bee venoms 8) and ubiquitous tissues. 9 14,17,18) This accords with their branching patterns, in the phylogenetic tree. 19) Mathematical examination of the nucleotide sequences of their cDNAs and genes has revealed that they evolved via Darwinian-type accelerated evolution, acquiring diverse physiological activities.…”

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

“…Disruptions in PLA 2 are often associated with impairment in normal reproduction. For instance, defi ciency in sPLA 2 -III, which is expressed in proximal epididymal epithelium, causes defects in sperm maturation and impairment in the ability of the spermatozoa to fertilize intact eggs ( 193 ). These were associated with a compromised shift in acyl groups from oleic acid, linoleic acid, and AA to docosapentaenoic and docosahexaenoic acids during epididymal transit.…”

Les phospholipases, enzymes clés de la physiologie spermatique

“…De plus, plusieurs études ont montré que certaines asthénozoosper-mies (absence ou faible mobilité des spermatozoïdes [47] (➜) sont associées chez l'homme à une composition lipidique défectueuse, caractérisée par un excès de cholestérol et de desmostérol, une faible concentration d'acide gras polyinsaturés (dont l'acide docosahexaénoïque) et une augmentation du contenu en acides gras saturés [21,22]. Ces résultats indiquent que la composition lipidique est un élément crucial pour un fonctionnement optimal du flagelle, et que toute altération des enzymes impliquées dans le contrôle de la composition lipidique de la membrane plasmique peut entraîner une asthénozoospermie chez l'homme [21,22] et la souris [23]. Cette diminution de la mobilité pourrait être liée à une altération de la fluidité membranaire, qui est très dépendante de la composition en lipides.…”