Paternal high-fat diet altered SETD2 gene methylation in sperm of F0 and F1 mice

Abstract Paternal high-fat diet (HFD) can alter the epigenetics of sperm DNA, resulting in transmission obesity-related traits to offspring. Previous studies have mainly focused on HFD-induced changes DNA methylation imprinted genes, overlooking potential involvement non-imprinted genes this process. SETD2 , an important epigenetically-regulated gene known for its response environmental stress, remains poorly understood context diet-induced epigenetic changes. Here we examined effect obesity from a HFD paternal expression and sperm, embryos at blastocyst stage during subsequent development, determine alteration intergenerational transgenerational inheritance. The result showed that mice fed with two months had significantly increased testis sperm. altered level 20 26 CpG sites being changed F0 mice. apoptotic index decreased total cell number blastocysts, which were closely correlated Out sites, also found three F1 mice, meant these maintained. In conclusion, exposure disrupted pattern resulted perturbed expression. Furthermore, influenced embryo apoptosis possibly through pathway. induced by partially persisted generation, highlighting role as carrier