Both epidemiologic and experimental animal studies demonstrate that chronic psychological stress exerts adverse effects on the initiation and/or progression of many diseases. However, intergenerational effects of this environmental information remains poorly understood. Here, using a C57BL/6 mouse model of restraint stress, we show that offspring of stressed fathers exhibit hyperglycemia due to enhanced hepatic gluconeogenesis and elevated expression of PEPCK. Mechanistically, we identify an epigenetic alteration at the promoter region of the Sfmbt2 gene, a maternally imprinted polycomb gene, leading to a downregulation of intronic microRNA-466b-3p, which post-transcriptionally inhibits PEPCK expression. Importantly, hyperglycemia in F1 mice is reversed by RU486 treatment in fathers, and dexamethasone administration in F0 mice phenocopies the roles of restraint stress. Thus, we provide evidence showing the effects of paternal psychological stress on the regulation of glucose metabolism in offspring, which may have profound implications for our understanding of health and disease risk inherited from fathers.
Somatic cell nuclear transfer offers new opportunities for genetic engineering and genome preservation in mammalian animal species. We show that, in addition to cumulus cells, cultured adult rabbit fibroblasts are also capable of supporting full-term development after nuclear transfer. Nuclear transfer embryos constructed using serum-starved fibroblasts showed a significantly higher developmental rate than non-starved fibroblasts through preimplantation stages. A total of 467 nuclear transfer embryos were transferred into the oviducts of pseudo pregnant mothers. Eight of the 20 surrogate rabbits carried the pregnancy to term and five of them gave birth naturally to a total of nine rabbits. However, all of the offspring died before postnatal day 10. A Caesarean section was performed on three surrogates, giving birth to a total of five rabbits, three of them survived and grew into healthy adults. DNA analyses confirmed that these rabbits were genetically identical to the donor male rabbit. The present study demonstrates that rabbits can be cloned from adult fibroblasts after culture.
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