Lauby Samantha C, Agarwal Isha, Lapp Hannah E, Salazar Melissa, Semyrenko Sofiia, Chauhan Danyal, Margolis Amy E, Champagne Frances A
Department of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX, United States of America; Center for Molecular Carcinogenesis and Toxicology, University of Texas at Austin, Austin, TX, United States of America.
Department of Psychology, College of Liberal Arts, University of Texas at Austin, Austin, TX, United States of America.
Horm Behav. 2025 Jun;172:105745. doi: 10.1016/j.yhbeh.2025.105745. Epub 2025 Apr 23.
Prenatal exposure to endocrine disrupting chemicals, such as bisphenols, can alter neurodevelopmental trajectories and have a lasting neurobehavioral impact through epigenetic pathways. However, outcomes associated with prenatal bisphenol exposure may also be shaped by the postnatal environment and collectively these environmental effects may be sex-specific. Thus, an integrative research design that includes multiple early life exposures and considers sex differences may be essential for predicting outcomes. In the current study, we use a multivariate approach to examine the contributions of prenatal bisphenol exposure, postnatal maternal care, and offspring sex to variation in DNA methylation of well-studied candidate genes (NR3C1, BDNF, OXTR) in the ventral hippocampus and amygdala of adult Long-Evans rats. Main effects of postnatal maternal care and interactions with prenatal bisphenol exposure were consistently found for DNA methylation within the NR3C1 gene (ventral hippocampus) and within the BDNF and OXTR genes (amygdala). Sex-specific effects were also found across all analyses. Overall, our findings suggest that both early-life factors (prenatal and postnatal) and offspring sex contribute to variation in DNA methylation in genes and brain regions relevant for the expression of anxiety-like behavior. These results highlight the need to consider the brain region-specific effects of multiple exposures in males and females to understand the lasting effects of early environments.
产前暴露于内分泌干扰化学物质（如双酚类）可改变神经发育轨迹，并通过表观遗传途径产生持久的神经行为影响。然而，与产前双酚暴露相关的结果也可能受到产后环境的影响，而且这些环境影响可能具有性别特异性。因此，一种综合研究设计，包括多种早期生活暴露并考虑性别差异，对于预测结果可能至关重要。在当前研究中，我们采用多变量方法来检验产前双酚暴露、产后母性照料以及子代性别对成年Long-Evans大鼠腹侧海马体和杏仁核中研究充分的候选基因（NR3C1、BDNF、OXTR）DNA甲基化变化的影响。在NR3C1基因（腹侧海马体）以及BDNF和OXTR基因（杏仁核）内，持续发现产后母性照料的主效应以及与产前双酚暴露的相互作用。在所有分析中也发现了性别特异性效应。总体而言，我们的研究结果表明，早期生活因素（产前和产后）以及子代性别均会导致与焦虑样行为表达相关的基因和脑区DNA甲基化发生变化。这些结果凸显了考虑雄性和雌性中多种暴露的脑区特异性效应对于理解早期环境的持久影响的必要性。
