Department of Basic Nursing, School of Nursing, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
Anhui Medical College, Hefei, 230601, Anhui, China.
Sci Rep. 2023 May 17;13(1):7984. doi: 10.1038/s41598-023-31690-w.
The DOHaD theory suggests that adverse environmental factors in early life may lead to the development of metabolic diseases including diabetes and hypertension in adult offspring through epigenetic mechanisms such as DNA methylation. Folic acid (FA) is an important methyl donor in vivo and participates in DNA replication and methylation. The preliminary experimental results of our group demonstrated that lipopolysaccharide (LPS, 50 µg/kg/d) exposure during pregnancy could lead to glucose metabolism disorders in male offspring, but not female offspring; however, the effect of folic acid supplementation on glucose metabolism disorders in male offspring induced by LPS exposure remains unclear. Therefore, in this study, pregnant mice were exposed to LPS on gestational day (GD) 15-17 and were given three doses of FA supplementation (2 mg/kg, 5 mg/kg, or 40 mg/kg) from mating to lactation to explore its effect on glucose metabolism in male offspring and the potential mechanism. This study confirmed that FA supplementation of 5 mg/kg in pregnant mice improved glucose metabolism in LPS-exposed offspring during pregnancy by regulating gene expression.
DOHaD 理论表明,生命早期的不利环境因素可能通过表观遗传机制,如 DNA 甲基化,导致成年后代代谢疾病的发生,包括糖尿病和高血压。叶酸(FA)是体内重要的甲基供体,参与 DNA 复制和甲基化。我们小组的初步实验结果表明,孕期暴露于脂多糖(LPS,50μg/kg/d)可导致雄性后代葡萄糖代谢紊乱,但不影响雌性后代;然而,LPS 暴露诱导的雄性后代葡萄糖代谢紊乱补充叶酸的效果尚不清楚。因此,在这项研究中,我们在妊娠第 15-17 天对怀孕的老鼠进行 LPS 暴露,并在交配到哺乳期给予 3 次 FA 补充(2mg/kg、5mg/kg 或 40mg/kg),以探索其对 LPS 暴露雄性后代葡萄糖代谢的影响及其潜在机制。本研究证实,孕期给予母鼠 5mg/kg 的 FA 补充可通过调节基因表达改善 LPS 暴露后代的葡萄糖代谢。