Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice
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
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
View: Text | PDF
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

×

Figure 7

Blocking endogenous mGX sPLA2 with the specific inhibitor LY329722 impacts both fertility outcome and spontaneous AR.

Options: View larger image (or click on image) Download as PowerPoint
Blocking endogenous mGX sPLA2 with the specific inhibitor LY329722 impac...
(A) Endogenous mGX, secreted during spontaneous AR, controls the yield of viable embryos, without changing the rate of fertilization. IVF experiments were performed with either control sperm or the same sperm treated throughout capacitation with 1 μM LY329722 (n = 8) and unfertilized oocytes. Two-cell embryos and aborted embryos were scored. Inhibiting mGX decreases 2-cell embryos and increases aborted embryos. The design of the experiment clearly indicates that LY329722 controls the yield of viable embryos by inhibiting endogenous mGX secreted during spontaneous AR. (B) The sPLA2 inhibitor LY329722 blocked the late phase of spontaneous AR. Spontaneous AR was quantified during capacitation at 10, 55, and 90 minutes in the absence or presence of 1 μM LY329722 (n = 10–14). Incubation of sperm with 1 μM LPC during the last 45 minutes partially rescued the inhibition of spontaneous AR induced by LY329722 (n = 7).