Dietary Docosahexaenoic Acid Fully Restores Fertility and Spermiogenesis in the Male Delta‐6‐Desaturase Knockout Mouse

Abstract

Delta‐6 desaturase (D6D) is the rate limiting enzyme for the synthesis of highly unsaturated fatty acids (HUFAs): 20:4n6 arachidonic acid (AA), 22:6n3 docosahexaenoic acid (DHA), and 22:5n6 docosapentaenoic acid (DPA), all of which are abundant in murine spermatozoa. The D6D knockout (‐/‐) mouse, unable to synthesize HUFAs, is infertile by 6 weeks of age due to disrupted spermiogenesis and lack of spermatid elongation. In order to determine which HUFA is essential for spermiogenesis, AIN93G diet supplemented with either 0.2 % (w/w) AA or DHA was fed to wild type (+/+) and D6D ‐/‐ mice at weaning until 16 weeks of age (n=3‐5). Frequency of successful matings of DHA supplemented ‐/‐ (61%) was not statistically different vs +/+ on DHA. The success rate of AA supplemented ‐/‐ (38%) was lower though not significant vs +/+ on AA, but higher than non‐supplemented ‐/‐ (8%, p<0.05). DHA supplemented ‐/‐ had normal sperm count (116% of +/+) and motility, while AA supplemented ‐/‐ had normal sperm motility but significantly lower sperm count (39% of +/+, p < 0.05). Histology of DHA supplemented ‐/‐ showed restored spermiogenesis with mature sperm in epididymis, while AA supplemented ‐/‐ had partially restored spermatogenesis with mature and immature sperm in epididymis. In conclusion, dietary DHA fully restores male reproductive function in ‐/‐. Partial restoration by AA may be due to sparing of DPA from retroconversion to AA.Grant Funding SourceInternal