Dominant negative effect on male fertility and sperm maturation by haploinsufficiency of ELOVL2 in mouse
(English)Manuscript (preprint) (Other academic)
ELOVL2 is a member of the mammalian microsomal enzyme family (ELOVL) involved in the elongation of very long-chain fatty acids (VLCFAs) including polyunsaturated fatty acids (PUFAs). Specifically, ELOVL2 is suggested to mediate the rate-limiting condensation reaction in the elongation of PUFAs of C20 and C22 carbons in length. These PUFAs are required for various physiological functions including, regulation of the composition and fluidity of cell membranes, signalling and gene expression. Moreover, certain PUFAs can be oxygenated forming eicosanoids which are implicated in a variety of signalling pathways. The expression of Elovl2 is highest in testis and liver, but significant amounts of transcripts can also be found in kidney, brain, lung and white adipose tissue. Here, we show that ablation of Elovl2 in mice results in a complete absence of VLCPUFAs with 24-30 carbon atoms of the n-6 family in the testis, and that these fatty acids are indispensable for normal spermatogenesis and fertility. Ablation of Elovl2 was associated with a complete arrest of spermatogenesis with seminiferous tubule displaying only spermatogonia and primary spermatocytes without further germinal cells. The Elovl2+/- mice exhibited abnormal sperm morphology with rounded, condensed head, instead of the normal elongated and hooked head seen in wild-type mice. Intercrosses of Elovl2+/- mice displayed both pre- and post-meiotic deficiency of spermatogenesis. These results indicate a novel mechanism involving ELOVL2-derived fatty acids in mammalian spermatogenesis.
IdentifiersURN: urn:nbn:se:su:diva-34406OAI: oai:DiVA.org:su-34406DiVA: diva2:284668