PSXV-10 Poor Maternal Nutrition Impacts Mrna Expression of Epigenetic Factors in ram Offspring Liver

Abstract

Abstract Poor maternal nutrition (over- and restricted-feeding) alters growth and metabolism in offspring after birth; however, the mechanisms are not well understood. Epigenetics, the heritable changes in gene expression without altering the DNA sequence, is a possible mechanism. We hypothesized that mRNA expression of epigenetic factors in livers of male offspring would be altered as a result of poor maternal diet during gestation. Multiparous Dorset ewes (n = 46) pregnant with twins were fed 100%, 60% or 140% of NRC requirements from d 30 ± 0.02 of gestation until parturition. Male offspring are referred to as CON (n=12), RES (n=21), and OVER (n=13), respectively. Ram lambs were euthanized at d 284±1.82, and liver tissue was immediately snap-frozen. RNA was isolated from liver and gene expression was quantified using real-time (RT)-PCR. Epigenetic factors of interest included DNA methyltransferases (DNMT; DNMT1, DNMT3B), ten eleven translocation enzyme 2 (TET2), lysine acetyltransferases (KAT; KAT1, KAT2B, KAT6A, KAT8), histone deacetylases (HDAC; HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC8, HDAC11, sirtuin1), and histone methyltransferases [ASH1 like histone lysine methyltransferase (ASH1L), euchromatic histone lysine methyltransferase (EHMT)1, EHMT2, SET domain bifurcated histone lysine methyltransferase 2 (SETDB2)]. Gene expression of ASH1L and KAT6A were decreased in liver tissue of RES compared with OVER by 42.8% and 59.7%, respectively (P≤0.017). Gene expression of DNMT1 and HDAC3 were decreased in RES compared with CON by 38.3% and 35.0%, respectively (P≤0.045). Gene expression of EHMT1 and HDAC8 were increased in OVER compared with CON by 19.3% and 37.4%, respectively (P≤0.045). There were no differences detected in expression of other genes (P≥0.060). Thus, maternal diet affects hepatic mRNA expression of specific epigenetic factors which may contribute to altered metabolism and liver function. Further investigation is warranted to determine how epigenetic modifications impact offspring growth and metabolism long-term.