Maternal Exposure to Organochlorine Pesticides and Epigenetic Alterations in Unexplained Recurrent Miscarriage

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INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.

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