Organochlorine pesticides and epigenetic alternations in unexplained female infertility

Epigenetic alterations could potentially have a significant impact on the adverse reproductive consequences in connection with exposure to environmental contaminants. In this study, the changes in Thyroid Stimulating Hormone Receptor (TSHR) and Ataxia Telangiectasia Mutated (ATM) genes methylation related to exposure to certain Organochlorine Pesticides (OCLs) in women with unexplained female infertility (UFI) were investigated. Promoter methylation of TSHR and ATM genes was conducted using methylation specific PCR in blood from 113 UFI and 103 controls. The methylation percentage of the TSHR was 48 % in UFI and 50 % in controls and the difference was statistically insignificant. But, promoter methylation of ATM was significantly higher in UFI than controls (67.9 % and 43.3 % respectively, p = 0.042). Logistic regression analysis also revealed that some OCLs (2,4-DDE, γ-HCH, 2,4-DDT, β-HCH, 4,4-DDT, and 4,4-DDE) affected methylation of ATM promoter. Among total OCLs, there were significant correlations between the ATM promoter methylation and Ʃ3 HCH, Σ2 DDE, and Ʃ7 OCLs in an adjusted model. The study posits that OCLs could modify epigenetic markers, thereby impacting gene function. Hypermethylation of the ATM gene in UFI cases, and its association with selected and total OCLs, underscores the detrimental effects of the accumulation of environmental stressors on female reproductive health, potentially leading to UFI. Furthermore, the role of ATM-mediated DNA Double-Strand Break repair in reproductive health was highlighted. Additionally, this research underscores the need for further investigation into the relationship between ATM gene promoter methylation, pesticide exposure, and UFI across various populations.