Disruption of androgen receptor signaling by chlorpyrifos (CPF) and its environmental degradation products: a structural insight

Hazarika, Jnyandeep; Ganguly, Mausumi; Borgohain, Gargi; Sarma, Shruti; Bhuyan, Pranjal; Mahanta, Rita

doi:10.1080/07391102.2021.1875885

Cited by 10 publications

(6 citation statements)

References 52 publications

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“…It resulted in a sex-specific increase of the ER-alpha/ER-beta ratio in males. Provided the expression change was reflected at protein level, this effect might have facilitated estrogenic actions of bisphenol A, PCBs or their metabolites, and chlorpyrifos ( Hazarika et al, 2020 ). Yet, the inverse dose-response exhibited by ER-alpha in males and, in the case of 0.5 mg/kg bisphenol A, also in females, makes a direct link to the changes in downstream genes doubtful.…”

Section: Discussionmentioning

confidence: 99%

“…Aro interacts with thyroid hormones in developing brain ( Gauger et al, 2004 ), and contains estrogenic congeners ( Decastro et al, 2006 ). The acetylcholinesterase inhibitor CPF exerts non-endocrine effects on nerve cells, but has also been found to exhibit estrogenic activity, and to affect thyroid hormone levels in brain ( Andersen et al, 2002 ; Slotkin and Seidler, 2009 ; Ventura et al, 2012 ; Slotkin et al, 2013 ; Hazarika et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences

et al. 2021

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Endocrine disrupting chemicals (EDCs) can impair hippocampus-dependent behaviors in rat offspring and in children. In search for key processes underlying this effect, we compared the transcriptomes of rat hippocampus on postnatal day 6 after gestational and lactational exposure to three different EDCs at doses known to impair development of learning and memory. Aroclor 1254, a commercial PCB mixture (5 mg/kg or 0.5 mg/kg), or bisphenol A (5 mg/kg or 0.5 mg/kg) were administered in chow, chlorpyrifos (3 mg/kg or 1 mg/kg) was injected subcutaneously. Male hippocampus exhibited a common effect of all three chemicals on genes involved in cell-autonomous processes, Sox6, Sox11, Pou2f2/Oct2, and Pou3f2/Brn2, all upregulated at the high dose. Additional genes of the Sox and Pou families were affected by only one or two of the chemicals. Real time RT PCR showed a comparable expression change for bisphenol A also at the lower dose. Female hippocampus exhibited much fewer genes with expression changes (almost none with false discovery rate <0.05), and none of the genes of the Sox and Pou families was affected. Since gene network analyses in male hippocampus suggested a link between Sox6 and miR-24, known to be repressed by activation of ER-alpha and to repress Sox6 in other tissues, this microRNA was measured. miR-24 was downregulated by all chemicals at the high dose in males. Values of Sox6 mRNA and miR-24 were inversely correlated in individual male hippocampus samples, supporting the hypothesis that the change in Sox6 expression resulted from an action of miR-24. In contrast, miR-24 levels remained unchanged in hippocampus of females. A sexually dimorphic response of miR-24 may thus be at the basis of the sex difference in Sox6 expression changes following exposure to the three chemicals. ER-alpha expression was also sex-dependent, but the expression changes did not parallel those of potential downstream genes such as Sox6. Sox6 is known to suppress differentiation of Parvalbumin (Pvalb)-expressing interneurons. Individual Sox6 levels (FPKM) were inversely correlated with levels of Pvalb, but not with markers of Sox6-independent interneuron subpopulations, Nos1 and 5HT3aR. Effects on interneuron development are further suggested, in males, by expression changes of Nrg1 and its receptor Erbb4, controlling interneuron migration. Our study disclosed new types of EDC-responsive morphogenetic genes, and illustrated the potential relevance of microRNAs in sexually dimorphic EDC actions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences

et al. 2021

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“…Concerning the former, some intensively used pesticides, like glyphosate, were shown to interfere with estrogen and androgen biosynthesis or signaling [18][19]. Bisphenol compounds, as well, can bind to estrogen receptors.…”

Section: Biological Targets Of Ed Activitymentioning

confidence: 99%

“…This produces conformational changes in the AR ligand binding domain, interfering with the binding of the endogenous AR ligand. [19]. Halogen bonding is also responsible for the high binding affinity of CPF towards serum albumin [9].…”

Section: Role Of Noncovalent Interactions In Ed Recognitionmentioning

confidence: 99%

Endocrine-disrupting pollutants properties affecting their bioactivity, remediation, and detection

Dichiarante

Cavallo

Metrangolo

2021

Current Opinion in Green and Sustainable Chemistry

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“…Researchers have found that CPY can cause liver and gill tissue damage in carp with low concentrations in aquatic environments [ 9 ]. Furthermore, once exposed in CPY, humans and animals can also cause reproductive and developmental neurotoxicity risks [ 10 , 11 , 12 , 13 ]. Because of the persistence and potential ecological hazards of CPY in water environments, methods for its removal have been attracted considerable attention.…”

Section: Introductionmentioning

confidence: 99%

Persulfate–Based Advanced Oxidation Process for Chlorpyrifos Degradation: Mechanism, Kinetics, and Toxicity Assessment

Xu,

Zhang,

Zou

et al. 2024

Toxics

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Persulfate-based advanced oxidation process has been proven to be a promising method for the toxic pesticide chlorpyrifos (CPY) degradation in wastewater treatment. However, due to the limitation for the short-lived intermediates detection, a comprehensive understanding for the degradation pathway remains unclear. To address this issue, density functional theory was used to analyze the degradation mechanism of CPY at the M06-2X/6-311++G(3df,3pd)//M06-2X/6-31+G(d,p) level, and computational toxicology methods were employed to explore the toxicity of CPY and its degradation products. Results show that hydroxyl radicals (·OH) and sulfate radicals (SO4•−) initiate the degradation reactions by adding to the P=S bond and abstracting the H atom on the ethyl group, rather than undergoing α-elimination of the pyridine ring in the persulfate oxidation process. Moreover, the addition products were attracted and degraded by breaking the P–O bond, while the abstraction products were degraded through dealkylation reactions. The transformation products, including 3,5,6-trichloro-2-pyridynol, O,O-diethyl phosphorothioate, chlorpyrifos oxon, and acetaldehyde, obtained through theoretical calculations have been detected in previous experimental studies. The reaction rate constants of CPY with ·OH and SO4•− were 6.32 × 108 and 9.14 × 108 M−1·s−1 at room temperature, respectively, which was consistent with the experimental values of 4.42 × 109 and 4.5 × 109 M−1 s−1. Toxicity evaluation results indicated that the acute and chronic toxicity to aquatic organisms gradually decreased during the degradation process. However, some products still possess toxic or highly toxic levels, which may pose risks to human health. These research findings contribute to understanding the transformation behavior and risk assessment of CPY in practical wastewater treatment.

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Disruption of androgen receptor signaling by chlorpyrifos (CPF) and its environmental degradation products: a structural insight

Cited by 10 publications

References 52 publications

Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences

Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences

Endocrine-disrupting pollutants properties affecting their bioactivity, remediation, and detection

Persulfate–Based Advanced Oxidation Process for Chlorpyrifos Degradation: Mechanism, Kinetics, and Toxicity Assessment

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