Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice
Jessica Escoffier, … , Gérard Lambeau, Christophe Arnoult
Jessica Escoffier, … , Gérard Lambeau, Christophe Arnoult
Published April 26, 2010
Citation Information: J Clin Invest. 2010;120(5):1415-1428. https://doi.org/10.1172/JCI40494.
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Research Article

Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice

Abstract

Ejaculated mammalian sperm must undergo a maturation process called capacitation before they are able to fertilize an egg. Several studies have suggested a role for members of the secreted phospholipase A2 (sPLA2) family in capacitation, acrosome reaction (AR), and fertilization, but the molecular nature of these enzymes and their specific roles have remained elusive. Here, we have demonstrated that mouse group X sPLA2 (mGX) is the major enzyme present in the acrosome of spermatozoa and that it is released in an active form during capacitation through spontaneous AR. mGX-deficient male mice produced smaller litters than wild-type male siblings when crossed with mGX-deficient females. Further analysis revealed that spermatozoa from mGX-deficient mice exhibited lower rates of spontaneous AR and that this was associated with decreased in vitro fertilization (IVF) efficiency due to a drop in the fertilization potential of the sperm and an increased rate of aborted embryos. Treatment of sperm with sPLA2 inhibitors and antibodies specific for mGX blocked spontaneous AR of wild-type sperm and reduced IVF success. Addition of lysophosphatidylcholine, a catalytic product of mGX, overcame these deficiencies. Finally, recombinant mGX triggered AR and improved IVF outcome. Taken together, our results highlight a paracrine role for mGX during capacitation in which the enzyme primes sperm for efficient fertilization and boosts premature AR of a likely phospholipid-damaged sperm subpopulation to eliminate suboptimal sperm from the pool available for fertilization.

Authors

Jessica Escoffier, Ikram Jemel, Akemi Tanemoto, Yoshitaka Taketomi, Christine Payre, Christelle Coatrieux, Hiroyasu Sato, Kei Yamamoto, Seiko Masuda, Karin Pernet-Gallay, Virginie Pierre, Shuntaro Hara, Makoto Murakami, Michel De Waard, Gérard Lambeau, Christophe Arnoult

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Figure 3

The lack of mGX sPLA2 in sperm affects male fertility.

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The lack of mGX sPLA2 in sperm affects male fertility. (A) The litte...
(A) The litter sizes of intercrosses between male and female mGX-deficient mice are lower than those of littermate WT mice. Note that male and female mGX–/– mice produced normal litter size when mated with WT C57BL/6J mice (B) Pictures of the different stages obtained after IVF at 24 hours: unfertilized oocytes; 2-cell embryos (normal development); aborted embryos corresponding to oocytes with either multiple and uncontrolled divisions or presenting a second polar body (2 PB) but no cell division (arrows). Scale bars: 50 μm. (C) Images of embryo development 24 hours after fertilization: +/+, WT sperm crossed with WT oocytes; –/–, mGX–/– sperm crossed with WT oocytes; arrows show unfertilized oocytes and asterisks show aborted embryos. (D) IVFs performed with mGX–/– sperm and WT oocytes have a lower rate of 2-cell embryos and higher rate of aborted embryos compared with IVFs performed with sperm from WT (+/+) or heterozygous (+/–) littermates and WT oocytes (n = 11). (E) The low fertilizing potential of mGX–/– sperm is rescued by recombinant mGX. IVF was performed by mixing WT oocytes with (a) WT sperm from littermates (n = 4); (b) mGX–/– sperm (n = 4); or (c) mGX–/– sperm briefly treated with 200 nM mGX (treatment for 10 minutes at the end of the capacitation period [gray bars, n = 4]). The development of eggs was evaluated after 24 hours by counting the different stages.