母体暴露于有机氯农药与不明原因复发性流产中的表观遗传改变
Maternal Exposure to Organochlorine Pesticides and Epigenetic Alterations in Unexplained Recurrent Miscarriage.
摘要(中文译文)
有机氯农药（OClPs）是能够影响生殖健康的环境污染物。不明原因复发性流产（URM）的病因尚未完全阐明，但一些证据表明，胎儿和胎盘组织的表观基因组可能是其原因。本研究旨在建立OClP暴露与这些组织中TSHR和ATM启动子甲基化之间的相关性。这项横断面病例对照研究共纳入73名URM女性和30名对照者，采集了血液、胎儿及胎盘组织样本。采用气相色谱法测定血清中OClPs（4,4-DDE、α-HCH、2,4-DDE、γ-HCH、4,4-DDT、β-HCH和2,4-DDT）的水平，并使用甲基化特异性PCR评估胎盘和胎儿样本中ATM和TSHR启动子的甲基化状态。同时采用逻辑回归分析检验OClP暴露与所选基因DNA甲基化之间的关联。与对照组相比，URM病例中4,4-DDE、2,4-DDE、β-HCH、α-HCH及总OClPs（Ʃ7OClP、Ʃ2DDT、Ʃ2DDE和Ʃ3HCH）水平显著升高。两组之间TSHR启动子甲基化无显著差异。另一方面，与对照组（83.3%）相比，URM胎盘组织中观察到ATM启动子低甲基化（45.8%，p = 0.015），且与2,4-DDT和Ʃ2DDT水平升高显著相关。暴露于OClPs，尤其是2,4-DDT和Ʃ2DDT，有可能通过使ATM启动子低甲基化来干扰胎盘DNA修复过程，从而可能促进URM的发病机制。此外，这些结果强调了表观遗传改变的组织特异性特征，并突出了环境暴露与生殖健康结局之间复杂的相互作用。本研究表明，OClP诱导的表观遗传改变在胎盘DNA修复机制中发挥关键作用，并可能参与不明原因复发性流产的病理生理过程。
Abstract
Organochlorine Pesticides (OClPs) are environmental pollutants that can affect reproductive health. Unexplained Recurrent Miscarriage (URM) has not been fully clarified, but some evidence suggests that the epigenome of fetal and placental tissues could be the cause. This study aimed to establish the correlation between OClP exposure and methylation of the TSHR and ATM promoters in these tissues. Blood, fetal, and placental tissues were sampled in this cross-sectional casecontrol study involving 73 women with URM and 30 controls. Gas chromatography was used to determine serum levels of OClPs (4,4-DDE, α-HCH, 2,4-DDE, γ-HCH, 4,4-DDT, β-HCH, and 2,4-DDT), and the determination of ATM and TSHR promoters' methylation in placental and fetal samples was assessed using Methylation-specific PCR. Logistic regression analysis was also used to test associations between OClP exposure and DNA methylation of the selected genes. 4,4-DDE, 2,4-DDE, β-HCH, α-HCH, and total OClPs (Ʃ7OClP, Ʃ2DDT, Ʃ2DDE, and Ʃ3HCH) were significantly higher in URM cases compared to controls. There were no significant differences in TSHR promoter methylation between the groups. On the other hand, ATM promoter hypomethylation was observed in URM placental tissues (45.8%) compared with controls (83.3%, p = 0.015) and was significantly associated with increased levels of 2,4-DDT and Ʃ2DDT. Exposure to OClPs, particularly 2,4-DDT and Ʃ2DDT, has the potential to interfere with placental DNA repair processes by hypomethylating the ATM promoter and thus potentially contribute to the pathogenesis of URM. Furthermore, these results emphasize the tissue-specific characteristics of epigenetic changes and highlight the complex interactions between environmental exposures and reproductive health outcomes. This study demonstrates the critical role of OClP-induced epigenetic alterations in the placental DNA repair mechanisms and their possible contribution to the pathophysiology of unexplained recurrent miscarriage.
如何引用
AMA
Sanaz Faramarz, Gholamreza Asadikaram, Mojtaba Abbasi-Jorjandi, Moslem Abolhassani, Mohammad Hadi Nematollahi, Mohammad Erfan Norouzmahani, et al. Maternal Exposure to Organochlorine Pesticides and Epigenetic Alterations in Unexplained Recurrent Miscarriage.. Current medicinal chemistry. 2026; doi:10.2174/0109298673429987260225080706.
APA
Sanaz Faramarz, Gholamreza Asadikaram, Mojtaba Abbasi-Jorjandi, Moslem Abolhassani, Mohammad Hadi Nematollahi, Mohammad Erfan Norouzmahani, et al (2026). Maternal Exposure to Organochlorine Pesticides and Epigenetic Alterations in Unexplained Recurrent Miscarriage.. Current medicinal chemistry. https://doi.org/10.2174/0109298673429987260225080706
GB/T 7714
Sanaz Faramarz, Gholamreza Asadikaram, Mojtaba Abbasi-Jorjandi, Moslem Abolhassani, Mohammad Hadi Nematollahi, Mohammad Erfan Norouzmahani, et al. Maternal Exposure to Organochlorine Pesticides and Epigenetic Alterations in Unexplained Recurrent Miscarriage.[J]. Current medicinal chemistry, 2026 doi:10.2174/0109298673429987260225080706.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出