Effects of Gestational Arsenic Exposures on Placental and Fetal Development in Mice: The Role of Cyr61 m6A

作者：Yaping Song, Jin-Wei Lv, Zhicheng Zhang, Qing-Hua Qian, Yijun Fan, Daozhen Chen, Heng Zhang, Feixiang Xu, Cheng Zhang, Yichao Huang, Hua Wang, Wei Wei, De‐Xiang Xu · 发表于：Environmental Health Perspectives · 年份：2023 · DOI：10.1289/ehp12207 · 被引用次数：38 · 研究领域：RNA modifications and cancer、MicroRNA in disease regulation、Arsenic contamination and mitigation

Background: Several epidemiological investigations demonstrated that maternal arsenic (As) exposure elevated risk of fetal growth restriction (FGR), but the mechanism remains unclear. Objectives: This study aimed to investigate the effects of gestational As exposure on placental and fetal development and its underlying mechanism. Methods: Dams were exposed to 0.15, 1.5, and 15mg/L NaAsO2 throughout pregnancy via drinking water. Sizes of fetuses and placentas, placental histopathology, and glycogen content were measured. Placental RNA sequencing was conducted. Human trophoblasts were exposed to NaAsO2 (2μM) to establish an in vitro model of As exposure. The mRNA stability and protein level of genes identified through RNA sequencing were measured. N6-Methyladenosine (m6A) modification was detected by methylated RNA immunoprecipitation–quantitative real-time polymerase chain reason (qPCR). The binding ability of insulin-like growth factor 2 binding protein 2 to the gene of interest was detected by RNA-binding protein immunoprecipitation-qPCR. Intracellular S-adenosylmethionine (SAM) and methyltransferase activity were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and colorimetry, respectively. In vitro As+3 methyltransferase (As3MT) knockdown or SAM supplementation and in vivo folic acid (FA) supplementation were used to evaluate the protective effect. A case–control study verified the findings. Results: Sizes of fetuses (exposed to 1.5 and 15mg/L ...