Pesticide-induced epigenetic suppression of WNT signaling and NF-κB-driven inflammation impairs ovarian function in rats

The study examined the impact of chlorpyrifos, dimethoate, and their co-exposure on ovarian structure and function in female Wistar rats. The study involved 24 rats, divided into four groups: control, chlorpyrifos (3 mg/kg), dimethoate (30 mg/kg), and combination. Histopathology revealed degenerated...

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Published in:Food and chemical toxicology Vol. 205; p. 115706
Main Authors: Jan, Jasmeena, Sheikh, Wajid Mohammad, Gul, Shazia, Mohidin, Rumaisa, Bhat, Owais Mohmad, Lone, Mohammad Nadeem, Shah, Showkat Ahmad, Dar, Abid Hamid, Zargar, Mohammad Afzal, Bashir, Showkeen Muzamil, Wani, Nissar Ahmad
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.11.2025
Subjects:
Animals
Chlorpyrifos
Chlorpyrifos - toxicity
Dimethoate
DNA methylation
DNA Methylation - drug effects
Epigenesis, Genetic - drug effects
Female
Hormonal imbalance
Inflammation
Inflammation - chemically induced
Inflammation - genetics
Inflammation - metabolism
NF-kappa B - genetics
NF-kappa B - metabolism
Ovarian function
Ovary - drug effects
Ovary - metabolism
Ovary - pathology
Ovary - physiopathology
Pesticides - toxicity
Rats
Rats, Wistar
Wnt Signaling Pathway - drug effects
Chlorpyrifos
DNA methylation
Inflammation
Ovarian function
Dimethoate
Hormonal imbalance
ISSN:0278-6915, 1873-6351, 1873-6351
Online Access:Get full text
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Summary:The study examined the impact of chlorpyrifos, dimethoate, and their co-exposure on ovarian structure and function in female Wistar rats. The study involved 24 rats, divided into four groups: control, chlorpyrifos (3 mg/kg), dimethoate (30 mg/kg), and combination. Histopathology revealed degenerated and atretic follicles, disorganized granulosa cells and cystic follicles in pesticide exposed rats. Hormonal analysis showed decrease in FSH, LH, PG, T and AMH and increase in ED levels. Gene expression studies revealed significant upregulation of ESR2 (∼2, ∼1.8, and ∼1.85 fold respectively) in chlorpyrifos, dimethoate and combination groups. In contrast, RSPO2, WNT7A, WNT3A and WNT5A were downregulated (reduced by ∼1.73–1.8, 1.7–2.6, 1.45–2.13 and 1.3–1.75 fold, respectively). The changes correlated with reduced β-catenin activation. DNA methylation analysis revealed an inverse correlation between methylation and gene expression, alongside upregulation of DNMT3A and DNMT3B (∼4.5, ∼2.1, ∼4.9; ∼3.75, ∼2.2, ∼3.8 fold in chlorpyrifos, dimethoate and combination groups respectively), suggesting methylation-mediated repression. Furthermore, enhanced expression of inflammation-related genes and cytokines, coupled with NF-κB activation, indicated significant inflammatory responses. Overall, the findings highlight gene specific DNA methylation and inflammatory disruptions in pesticide-exposed ovaries. However, the lack of ChIP assay limits confirmation of DNMT recruitment, which should be addressed in future studies. [Display omitted]
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ISSN:0278-6915
1873-6351
1873-6351
DOI:10.1016/j.fct.2025.115706