Testis-specific knockout of Elovl4 reduces sperm motility and fertility in male mice

Fatty acid elongase 4 (Elovl4) is a crucial enzyme in mammals for synthesizing very long-chain fatty acids (VLC-FAs) with more than 26 carbons in a few specific tissues. In the testis and the sperm produced therefrom, the primary elongation products of Elovl4 are very long-chain polyunsaturated fatty acids (VLC-PUFAs), and previous studies have suggested that they may play a significant role in male reproduction. However, it remains unclear how Elovl4 and its elongation products, VLC-PUFAs, affect male fertility. This study is the first to systematically investigate the impact of testicular Elovl4 deletion on male fertility and its molecular mechanisms using a mouse model with testis-specific knockout of the Elovl4 gene (Elovl4[flox/flox], Stra8-cre). Our research demonstrates that the biosynthesis of VLC-PUFAs with more than 26 carbons is absent in the testes of Elovl4[flox/flox], Stra8-cre mice, leading to abnormal spermatogenesis, reduced sperm count, and sperm malformation. More notably, the specific knockout of this gene causes drastic changes in the expression levels of multiple members of the Defbs gene family in the testes and a significant decrease in sperm motility. This ultimately led to a sharp decline in the fertility of Elovl4[flox/flox], Stra8-cre male mice.