Male mice that do not express group VIA phospholipase A2 produce spermatozoa with impaired motility and have greatly reduced fertility

The Journal of Biological Chemistry
Shunzhong BaoJohn Turk

Abstract

The Group VIA Phospholipase A(2) (iPLA(2)beta) is the first recognized cytosolic Ca(2+)-independent PLA(2) and has been proposed to participate in arachidonic acid (20:4) incorporation into glycerophosphocholine lipids, cell proliferation, exocytosis, apoptosis, and other processes. To study iPLA(2)beta functions, we disrupted its gene by homologous recombination to generate mice that do not express iPLA(2)beta. Heterozygous iPLA(2)beta(+/-) breeding pairs yield a Mendelian 1:2:1 ratio of iPLA(2)beta(+/+), iPLA(2)beta(+/-), and iPLA(2)beta(-/-) pups and a 1:1 male:female gender distribution of iPLA(2)beta(-/-) pups. Several tissues of wild-type mice express iPLA(2)beta mRNA, immunoreactive protein, and activity, and testes express the highest levels. Testes or other tissues of iPLA(2)beta(-/-) mice express no iPLA(2)beta mRNA or protein, but iPLA(2)beta(-/-) testes are not deficient in 20:4-containing glycerophosphocholine lipids, indicating that iPLA(2)beta does not play an obligatory role in formation of such lipids in that tissue. Spermatozoa from iPLA(2)beta(-/-) mice have reduced motility and impaired ability to fertilize mouse oocytes in vitro and in vivo, and inhibiting iPLA(2)beta with a bromoenol lactone suicide substr...Continue Reading

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