Intergenerational and transgenerational effects of environmental factors and a role for the epigenome

Palakodety, Niharika; Gardner, Amaree J.; Fry, Rebecca C.

doi:10.1016/b978-0-12-819968-8.00014-7

Cited by 2 publications

(4 citation statements)

References 175 publications

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“…Vinclozolin [3-(3,5-dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione] is a fungicide widely used in Europe and the United States [ 8 ] in the control of Sclerotinia sclerotiorum, Monilinia spp., and Botrytis cinerea on vegetables, fruits, vines, and ornamental plants [ 9 ]. In particular, it is the most frequently fungicide used by the wine industry [ 10 ]. Many papers in the literature indicate vinclozolin as an environmental and aquatic pollutant [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Chronic Exposure to Vinclozolin Induced Fibrosis, Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Mice Kidney

Paola

D’Amico

Genovese

et al. 2022

IJMS

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Vinclozolin is one of the most used fungicides in the control of fungi in fruits, vegetables, and ornamental plants. The effects of its exposure on different organs have been described, but information regarding its relevance to vinclozolin-induced nephrotoxicity is largely missing. This study focuses on the potential mechanism of vinclozolin-induced nephrotoxicity. CD1 male mice were administered vinclozolin (100 mg/kg) by oral gavage for 28 days. Vinclozolin administration decreased body weight over the treatment period and at the end of the experiment, increased the ratio of kidney weight to body weight and increased serum urea nitrogen and creatinine contents. Vinclozolin also induced histopathological alterations, including tubular dilatation and necrosis and impaired the integrity of the renal-tubular architecture and kidney fibrosis. The analyses conducted showed that vinclozolin administration altered the mRNA levels of mitochondrial function-related proteins (SIRT3, SIRT1, PGC-1α, TFAM, NRF1, VDAC-1, and Cyt c) and oxidative stress (increased lipid peroxidation and decreased total antioxidative capacity, catalase, and superoxide dismutase activities, glutathione levels, and glutathione peroxidase activity) in the kidneys. Furthermore, vinclozolin induced toxicity that altered Nrf2 signalling and the related proteins (HO-1 and NQO-1). Vinclozolin administration also affected both the extrinsic and intrinsic apoptotic pathways, upregulating the expression of proapoptotic factors (Bax, Caspase 3, and FasL) and downregulating antiapoptotic factor (Bcl-2) levels. This study suggests that vinclozolin induced nephrotoxicity by disrupting the transcription of mitochondrial function-related factors, the Nrf2 signalling pathway, and the extrinsic and intrinsic apoptotic pathways.

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Section: Introductionmentioning

confidence: 99%

Chronic Exposure to Vinclozolin Induced Fibrosis, Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Mice Kidney

Paola

D’Amico

Genovese

et al. 2022

IJMS

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“…Vinclozolin is an antiandrogenic fungicide that has been implicated in disruption of sexual differentiation and reproductive function 51 . While there is no existing evidence that vinclozolin is linked to nervous system disease, it has been found to promote epigenetic transgenerational effects, which could influence individual differences in drug response 52 , modify responses to other exposures, or influence disease inheritance 51 . Therefore, future analyses should consider the role of vinclozolin—potentially in combination with other pesticides—in differential development of Alzheimer’s disease, multiple sclerosis, and Parkinson disease.…”

Section: Discussionmentioning

confidence: 99%

“…Vinclozolin is an antiandrogenic fungicide that has been implicated in disruption of sexual differentiation and reproductive function 51 . While there is no existing evidence that vinclozolin is linked to nervous system disease, it has been found to promote epigenetic transgenerational effects, which could influence individual differences in drug response 52 , modify responses to other exposures, or influence disease inheritance 51 The primary limitation in our analysis is the assumption that pesticides used in a geographic region affect individuals living in that location. Likely routes of exposure are not considered (e.g., oral versus inhalation), nor the likelihood that an individual would come in contact with a pesticide based on its physicochemical properties (e.g., persistence).…”

Section: Discussionmentioning

confidence: 99%

“…For example, all three diseases implicated vincozolin with high risk based on pesticide usage (no low probability states had vinclozolin in an association rule), but vinclozolin was not linked to these diseases in our dataset. Vinclozolin is an antiandrogenic fungicide that has been implicated in disruption of sexual differentiation and reproductive function 51 . While there is no existing evidence that vinclozolin is linked to nervous system disease, it has been found to promote epigenetic transgenerational effects, which could influence individual differences in drug response 52 , modify responses to other exposures, or influence disease inheritance 51 The primary limitation in our analysis is the assumption that pesticides used in a geographic region affect individuals living in that location.…”

Section: Discussionmentioning

confidence: 99%

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Genetic variability in pathways associates with pesticide-induced nervous system disease in the United States

Kosnik,

Antczak,

Fantke

2023

Preprint

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Nervous system disease development following pesticide exposure can vary in a population, but genetic susceptibility to chemicals is poorly characterized. We developed a framework to build Chemical – SNP (single nucleotide polymorphism) – Disease linkages via biological pathways. We integrated these linkages with spatialized pesticide application data for the United States from 1992 – 2018 and nervous system disease rates for 2018 to characterize genetic variability in pesticide-induced nervous system disease. We found that the number of SNPs implicated per pesticide in US states positively correlates with disease incidence and prevalence for Alzheimer’s disease, Parkinson disease, and multiple sclerosis. Further, only 2% of pesticide sets used together over time overlapped between high disease occurrence and low disease occurrence states, with more SNPs implicated in pathways in high disease occurrence states. This supports that pesticides contribute to nervous system disease, and we developed priority lists of SNPs, pesticides, and pathways for further study.

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Intergenerational and transgenerational effects of environmental factors and a role for the epigenome

Cited by 2 publications

References 175 publications

Chronic Exposure to Vinclozolin Induced Fibrosis, Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Mice Kidney

Chronic Exposure to Vinclozolin Induced Fibrosis, Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Mice Kidney

Genetic variability in pathways associates with pesticide-induced nervous system disease in the United States

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