Oxidative Stress Mediated by N6-Methyladenosine Methylation Contributes to High-Fat Diet Induced Male Reproductive Dysfunction

ObjectiveTo determine the mechanism of oxidative stress mediated by N6-methyladenosine (m6A) methylation contributing to high fat diet-induced reproductive dysfunction. ResultsIn vivo, compared with those in the Control group, the sperm count and sperm motility decrease significantly; the testosterone, luteinizing hormone levels, hyaluronidase, acrosomal enzyme levels, and total antioxidant capacity decrease significantly; malondialdehyde increases significantly in the DIO and DIO-R groups. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1 (SOD1), and NAD(P)H quinone dehydrogenase 1 (NQO1) decreases significantly in the DIO and DIO-R groups; m6A levels in testis tissue in the DIO and DIO-R groups increase; the enrichment of m6A-modified Nrf2 mRNA in testis in the DIO group and DIO-R group increases significantly. Also the m6A regulatory proteins increase significantly in the DIO group and DIO-R group. In vitro, compared to palmitic acid treated cells, the reactive oxygen species (ROS) level significantly decreases in STM2457, S-Adenosylhomocysteine treated cells and YTHDC2, YTHDF2 gene silence cells; however, Nrf2 expression increases in all treated cells. In addition, m6A expression decreases. ConclusionsOxidative stress mediates by methylation of m6A may contribute to high fat diet-induced male reproductive dysfunction.

Automated summary

This study investigated the mechanism of oxidative stress mediated by N6-methyladenosine (m6A) methylation contributing to high fat diet-induced reproductive dysfunction. The results showed that high fat diet led to decreased sperm count, sperm motility, testosterone, luteinizing hormone levels, hyaluronidase, acrosomal enzyme levels, and total antioxidant capacity. Malondialdehyde levels increased while the expression of Nrf2, SOD1, and NQO1 decreased significantly. m6A levels in the testis tissue increased, along with an increase in m6A regulatory proteins. In vitro experiments showed that ROS levels decreased while Nrf2 expression increased in cells treated with S-Adenosylhomocysteine and gene silencing. Additionally, m6A expression decreased. Therefore, oxidative stress mediated by m6A methylation may contribute to high fat diet-induced male reproductive dysfunction.