Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, Smętna Street 12, 31-343 Kraków, Poland.
Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland.
Int J Mol Sci. 2021 Sep 7;22(18):9662. doi: 10.3390/ijms22189662.
Epidemiological and preclinical studies suggest that maternal obesity increases the risk of autism spectrum disorder (ASD) in offspring. Here, we assessed the effects of exposure to modified maternal diets limited to pregnancy and lactation on brain development and behavior in rat offspring of both sexes. Among the studied diets, a maternal high-fat diet (HFD) disturbed the expression of ASD-related genes (, , and ) and proteins (SHANK1 and TAOK2) in the prefrontal cortex of male offspring during adolescence. In addition, a maternal high-fat diet induced epigenetic changes by increasing cortical global DNA methylation and the expression of miR-423 and miR-494. As well as the molecular changes, behavioral studies have shown male-specific disturbances in social interaction and an increase in repetitive behavior during adolescence. Most of the observed changes disappeared in adulthood. In conclusion, we demonstrated the contribution of a maternal HFD to the predisposition to an ASD-like phenotype in male adolescent offspring, while a protective effect occurred in females.
流行病学和临床前研究表明，母体肥胖会增加后代患自闭症谱系障碍（ASD）的风险。在这里，我们评估了仅在妊娠和哺乳期暴露于改良的母体饮食对雄性和雌性大鼠后代大脑发育和行为的影响。在所研究的饮食中，母体高脂肪饮食（HFD）在青春期扰乱了雄性后代前额叶皮层中与 ASD 相关的基因（、和）和蛋白质（SHANK1 和 TAOK2）的表达。此外，母体高脂肪饮食通过增加皮质全基因组甲基化和 miR-423 和 miR-494 的表达诱导表观遗传变化。除了分子变化外，行为研究还表明，雄性在青春期表现出特定的社交互动障碍和重复行为增加。大多数观察到的变化在成年后消失。总之，我们证明了母体 HFD 对雄性青春期后代易患 ASD 样表型的贡献，而雌性则表现出保护作用。
