title: 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.
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.
authors.affiliation: The Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, Stockholm, Sweden.
authors.forename: Damir
authors.initials: D
authors.lastname: Zadravec
authors.forename: Petr
authors.initials: P
authors.lastname: Tvrdik
authors.forename: Hervé
authors.initials: H
authors.lastname: Guillou
authors.forename: Richard
authors.initials: R
authors.lastname: Haslam
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Johnathan A
authors.initials: JA
authors.lastname: Napier
authors.forename: Mario R
authors.initials: MR
authors.lastname: Capecchi
authors.forename: Anders
authors.initials: A
authors.lastname: Jacobsson
mesh_terms: D000123:Acetyltransferases / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000502:physiology; D008297:Male; D051379:Mice; D013079:Sperm Maturation; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis
chemical_list: D004042:Dietary Fats, Unsaturated; C000630951:ELOVL2 protein, mouse; D005231:Fatty Acids, Unsaturated; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases