Abstract
ELOVL2 is a member of the mammalian microsomal ELOVL fatty acid enzyme family, involved in the elongation of very long-chain fatty acids including PUFAs required for various cellular functions in mammals. Here, we used ELOVL2-ablated (Elovl2(-/-)) mice to show that the PUFAs with 24-30 carbon atoms of the ω-6 family in testis are indispensable for normal sperm formation and fertility in male mice. The lack of Elovl2 was associated with a complete arrest of spermatogenesis, with seminiferous tubules displaying only spermatogonia and primary spermatocytes without further germinal cells. Furthermore, based on acyl-CoA profiling, heterozygous Elovl2(+/-) male mice exhibited haploinsufficiency, with reduced levels of C28:5 and C30:5n-6 PUFAs, which gave rise to impaired formation and function of haploid spermatides. These new insights reveal a novel mechanism involving ELOVL2-derived PUFAs in mammals and previously unrecognized roles for C28 and C30 n-6 PUFAs in male fertility. In accordance with the function suggested for ELOVL2, the Elovl2(-/-) mice show distorted levels of serum C20 and C22 PUFAs from both the n-3 and the n-6 series. However, dietary supplementation with C22:6n-3 could not restore male fertility to Elovl2(+/-) mice, suggesting that the changes in n-6 fatty acid composition seen in the testis of the Elovl2(+/-) mice, cannot be compensated by increased C22:6n-3 content.
Highlights
ELOVL2 is a member of the mammalian microsomal elongation of very-long-chain fatty acid (ELOVL) fatty acid enzyme family, involved in the elongation of very long-chain fatty acids including PUFAs required for various cellular functions in mammals
Which resulted in a complete arrest of spermatogenesis, with seminiferous tubules displaying only spermatogonia and primary spermatocytes, without further germinal cells in male mice
Even more surprising is that heterozygote Elovl2+/Ϫ mice exhibited haploinsufficiency with reduced levels of n-6 C28:5 and C30:5 PUFAs, which gives rise to impaired packaging of haploid spermatides and infertility in almost all male mice, implying that even minor changes in Elovl2 expression and testicular omega-6 PUFA content may have severe effects on male reproduction ability
Summary
ELOVL2 is a member of the mammalian microsomal ELOVL fatty acid enzyme family, involved in the elongation of very long-chain fatty acids including PUFAs required for various cellular functions in mammals. Present evidence that ELOVL2 is essential for the formation of C24:5n-6 to C30:5n-6 PUFAs in testis and that these fatty acids are indispensable for normal spermatogenesis and fertility.
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