Paternal chronic folate supplementation induced transgenerational inheritance of acquired developmental and metabolic changes in chickens

Increasing evidence indicates that the paternal diet can result in offspring metabolic changes. A proposed mechanism for paternal transmission of environmental information is via the sperm noncoding RNAs, but the definite mechanism remains unclear in birds. We hypothesized that the dietary supplement of folate will alter noncoding RNAs expression profiles in sperm and further transgenerational regulate the metabolic process of offspring. Here, we fed breeder roosters with five different levels (0, 0.25, 1.25, 2.50, and 5.00 mg/kg) of folate throughout life, obtained the samples from breeder roosters and their offspring broilers, and further measured the development and metabolic indexes of breeder roosters and their offspring broilers. As results, different levels of paternal folate supplement were associated with the development changes in the offspring, which include the birth weight, postnatal feed conversion ratio, and the development of livers, bursa of fabricius, and small intestine. And mostly, the lipid and glucose metabolism process of offspring broilers could also be affected by the paternal dietary folate supplement, which has the similar effect with the metabolic changes in breeder roosters. Meanwhile, we employed global analyses of the hepatic mRNAs, lncRNAs, and miRNAs to test the effect of folate on the metabolic changes of breeder roosters and transgenerational effects of folate on offspring broilers. We found that some key genes involved in the glycolysis or gluconeogenesis and PPAR signaling pathway, such as PEPCK, ANGPTL4, and THRSP, could be regulated by the differentially expressed miRNAs and lncRNAs in the livers of breeder roosters and offspring broilers, which were induced by the dietary folate supplement of breeder roosters. Furthermore, global analyses of the breeder roosters’ sperm miRNAs and lncRNAs identified differentially expressed non-coding RNAs also implicated in the glycolysis or gluconeogenesis, PPAR signaling pathway, FOXO pathway, and several other lipid and glucose metabolism pathways as well. Overall, this model suggests dietary folate supplement could transgenerational regulate the lipid and glucose metabolism of offspring broilers and epigenetic transmission may involve the changes of miRNAs and lncRNAs expression profiles in sperm.