Cheng Yuting, Feng Jialin, Wang Jing, Zhou Yijie, Bai Shengjun, Tang Qiuqin, Li Jinhui, Pan Feng, Xu Qiaoqiao, Lu Chuncheng, Wu Wei, Xia Yankai
State Key Laboratory of Reproductive Medicine and Offspring Health, Wuxi Medical Center, Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Obstetrics, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.
Environ Res. 2024 Mar 1;244:117941. doi: 10.1016/j.envres.2023.117941. Epub 2023 Dec 15.
Paternal exposure to environmental risk factors influences the offspring health. This study aimed to evaluate the association between paternal air pollution exposure mediated by sperm DNA methylation and adverse birth outcomes in offspring. We recruited 1607 fertile men and their partners from 2014 to 2016 and collected semen samples to detect sperm DNA methylation. Multivariate linear regression and weighted quantile sum regression models were used to assess the associations between paternal air pollution exposure and offspring birth outcomes. A critical exposure window was identified. Reduced representation bisulfite sequencing was used to detect sperm DNA methylation. The results demonstrated that high paternal exposure to PM (β = -211.31, 95% CI: (-386.37, -36.24)), PM (β = -178.20, 95% CI: (-277.13, -79.27)), and NO (β = -84.22, 95% CI: (-165.86, -2.57)) was negatively associated with offspring's birthweight, especially in boys. Additionally, an early exposure window of 15-69 days before fertilization was recognized to be the key exposure window, which increased the risk of low birth weight and small for gestational age. Furthermore, paternal co-exposure to six air pollutants contributed to lower birthweight (β = -51.91, 95% CI: (-92.72, -11.10)) and shorter gestational age (β = -1.72, 95% CI: (-3.26, -0.17)) and PM was the most weighted pollutant. Paternal air pollution exposure resulted in 10,328 differentially methylated regions and the IGF2R gene was the key gene involved in the epigenetic process. These differentially methylated genes were predominantly associated with protein binding, transcriptional regulation, and DNA templating. These findings indicate that spermatogenesis is a susceptible window during which paternal exposure to air pollution affects sperm DNA methylation and the birth outcomes of offspring.
父亲暴露于环境危险因素会影响后代健康。本研究旨在评估精子DNA甲基化介导的父亲空气污染暴露与后代不良出生结局之间的关联。我们在2014年至2016年招募了1607名有生育能力的男性及其伴侣,并收集精液样本以检测精子DNA甲基化。采用多元线性回归和加权分位数和回归模型来评估父亲空气污染暴露与后代出生结局之间的关联。确定了一个关键暴露窗口。采用简化代表性亚硫酸氢盐测序来检测精子DNA甲基化。结果表明,父亲高暴露于PM(β = -211.31,95%CI:(-386.37,-36.24))、PM(β = -178.20,95%CI:(-277.13,-79.27))和NO(β = -84.22,95%CI:(-165.86,-2.57))与后代出生体重呈负相关,尤其是在男孩中。此外,受精前15 - 69天的早期暴露窗口被认为是关键暴露窗口,这增加了低出生体重和小于胎龄的风险。此外,父亲同时暴露于六种空气污染物会导致出生体重降低(β = -51.91,95%CI:(-92.72,-11.10))和孕周缩短(β = -1.72,95%CI:(-3.26,-0.17)),且PM是权重最大的污染物。父亲空气污染暴露导致10328个差异甲基化区域,IGF2R基因是参与表观遗传过程的关键基因。这些差异甲基化基因主要与蛋白质结合、转录调控和DNA模板化有关。这些发现表明,精子发生是一个易感窗口,在此期间父亲暴露于空气污染会影响精子DNA甲基化和后代的出生结局。