ELOVL2 controls the level of n-6 28:5 and 30:5 fatty acids in testis, a prerequisite for male fertility and sperm maturation in mice

Journal of Lipid Research

Richard Haslam¹  Johnathan A. Napier¹  Mario R. Capecchi²  Petr Tvrdik²  Hervé Guillou³  Tsutomu Kobayashi⁴  Damir Zadravec⁴  Anders Jacobsson⁵ 

[1] Department of Biological Chemistry, Rothamsted Research, Harpenden, United Kingdom;Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT;Laboratoire de Pharmacologie et Toxicologie, Institut National de la Recherche Agronomique, Toulouse, France;The Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, Stockholm, Sweden;To whom correspondence should be addressed.;

关键词: fatty acid elongase;    omega-6;    spermato­genesis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown