Ji Honglei, Zhu Haijun, Wang Ziliang, Liang Hong, Chen Yao, Liu Xiao, Yuan Wei, Wu Qihan, Yuan Zhengwei, Miao Maohua
Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200237, China.
Hubei Provincial Key Laboratory of Applied Toxicology, National Reference Laboratory of Dioxin, Hubei Provincial Center for Disease Control and Prevention, Wuhan, 430079, China.
Environ Res. 2025 Feb 1;266:120476. doi: 10.1016/j.envres.2024.120476. Epub 2024 Nov 28.
Prenatal exposure to bisphenol analogs (BPs) may pose hazards to offspring's health; however, their underlying mechanisms remain to be elucidated. DNA methylation, a major epigenetic mechanism, may be involved in early programming following environmental disturbances. In this prospective study, we investigated associations between prenatal BPs exposure and the placental DNA methylation levels of 14 candidate genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway among 205 mother-infant pairs and explored the potential mediating role of the DNA methylation in the association of prenatal BPs exposure with anthropometric measurements of infants aged 1 year. We observed a general pattern that prenatal BPs exposure was associated with the DNA hypomethylation of candidate genes, with associations consistently and notably observed for PPAR α (PPARA), retinoid X receptor α (RXRA), acetyl-CoA acyltransferase 1, and acyl-CoA dehydrogenase medium chain (ACADM) in linear regression and Bayesian kernel machine regression. Both models identified bisphenol F (BPF) as the predominant compound. We found inverse associations between the placental DNA methylation levels of most candidate genes, such as PPARA, RXRA, ACADM, and nuclear receptor subfamily 1 group H member 3 (NR1H3), and the length-for-age z-score, arm circumference-for-age z-score, subscapular skinfold-for-age z-score, and abdominal skinfold thickness of the infants. The DNA methylation levels of RXRA and NR1H3 could mediate the associations between prenatal BPF exposure and increased infant anthropometric measurements, with mediating portions ranging from 23.02% to 30.53%. Our findings shed light on the potential mechanisms underlying the effects of prenatal BPs exposure on infant growth and call for urgent actions for risk assessment and regulation of BPF. Future cohort studies with larger sample sizes are warranted to confirm our findings.
产前暴露于双酚类似物（BPs）可能对后代健康构成危害；然而，其潜在机制仍有待阐明。DNA甲基化是一种主要的表观遗传机制，可能参与环境干扰后的早期编程。在这项前瞻性研究中，我们调查了205对母婴中，产前BPs暴露与过氧化物酶体增殖物激活受体（PPAR）信号通路中14个候选基因的胎盘DNA甲基化水平之间的关联，并探讨了DNA甲基化在产前BPs暴露与1岁婴儿人体测量指标关联中的潜在中介作用。我们观察到一种普遍模式，即产前BPs暴露与候选基因的DNA低甲基化有关，在线性回归和贝叶斯核机器回归中，PPARα（PPARA）、视黄酸X受体α（RXRA）、乙酰辅酶A酰基转移酶1和酰基辅酶A脱氢酶中链（ACADM）的关联一致且显著。两种模型均确定双酚F（BPF）为主要化合物。我们发现大多数候选基因，如PPARA、RXRA、ACADM和核受体亚家族1组H成员3（NR1H3）的胎盘DNA甲基化水平与婴儿的年龄别身长Z评分、年龄别上臂围Z评分、年龄别肩胛下皮褶厚度Z评分和腹部皮褶厚度呈负相关。RXRA和NR1H3的DNA甲基化水平可介导产前BPF暴露与婴儿人体测量指标增加之间的关联，中介比例范围为23.02%至30.53%。我们的研究结果揭示了产前BPs暴露影响婴儿生长的潜在机制，并呼吁对BPF进行风险评估和监管采取紧急行动。未来需要进行更大样本量的队列研究来证实我们的发现。
