Dataset Information

Pre- and Postnatal Dietary Exposure to a Pesticide Cocktail Disrupts Ovarian Functions in 8-Week-Old Female Mice.

ABSTRACT: Female infertility has a multifactorial origin, and exposure to contaminants, including pesticides, with endocrine-disrupting properties is considered to be involved in this reproductive disorder, especially when it occurs during early life. Pesticides are present in various facets of the environment, and consumers are exposed to a combination of multiple pesticide residues through food intake. The consequences of such exposure with respect to female fertility are not well known. Therefore, we aimed to assess the impact of pre- and postnatal dietary exposure to a pesticide mixture on folliculogenesis, a crucial process in female reproduction. Mice were exposed to the acceptable daily intake levels of six pesticides in a mixture (boscalid, captan, chlorpyrifos, thiacloprid, thiophanate and ziram) from foetal development until 8 weeks old. Female offspring presented with decreased body weight at weaning, which was maintained at 8 weeks old. This was accompanied by an abnormal ovarian ultrastructure, a drastic decrease in the number of corpora lutea and progesterone levels and an increase in ovary cell proliferation. In conclusion, this study shows that this pesticide mixture that can be commonly found in fruits in Europe, causing endocrine disruption in female mice with pre- and postnatal exposure by disturbing folliculogenesis, mainly in the luteinisation process.

SUBMITTER: Dopavogui L

PROVIDER: S-EPMC9317375 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Pre- and Postnatal Dietary Exposure to a Pesticide Cocktail Disrupts Ovarian Functions in 8-Week-Old Female Mice.

Dopavogui Léonie L Cadoret Florence F Loison Gaspard G El Fouikar Sara S Frenois François-Xavier FX Giton Frank F Ellero-Simatos Sandrine S Lasserre Frédéric F Polizzi Arnaud A Rives Clémence C Loiseau Nicolas N Léandri Roger D RD Gatimel Nicolas N Gamet-Payrastre Laurence L

International journal of molecular sciences 20220707 14

Female infertility has a multifactorial origin, and exposure to contaminants, including pesticides, with endocrine-disrupting properties is considered to be involved in this reproductive disorder, especially when it occurs during early life. Pesticides are present in various facets of the environment, and consumers are exposed to a combination of multiple pesticide residues through food intake. The consequences of such exposure with respect to female fertility are not well known. Therefore, we a ...[more]

PMID: 35886873

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Project description:BackgroundEpidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at nonrelevant doses or in combination with other risk factors such as high-fat diets.ObjectivesWe aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at nontoxic doses, relevant to consumers' risk assessment.MethodsA mixture of six pesticides commonly used in France, i.e., boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram, was incorporated in a standard chow at doses exposing mice to the tolerable daily intake (TDI) of each pesticide. Wild-type (WT) and constitutive androstane receptor-deficient (CAR-/-) male and female mice were exposed for 52 wk. We assessed metabolic parameters [body weight (BW), food and water consumption, glucose tolerance, urinary metabolome] throughout the experiment. At the end of the experiment, we evaluated liver metabolism (histology, transcriptomics, metabolomics, lipidomics) and pesticide detoxification using liquid chromatography-mass spectrometry (LC-MS).ResultsCompared to those fed control chow, WT male mice fed pesticide chow had greater BW gain and more adiposity. Moreover, these WT males fed pesticide chow exhibited characteristics of hepatic steatosis and glucose intolerance, which were not observed in those fed control chow. WT exposed female mice exhibited fasting hyperglycemia, higher reduced glutathione (GSH):oxidized glutathione (GSSG) liver ratio and perturbations of gut microbiota-related urinary metabolites compared to WT mice fed control chow. When we performed these experiments on CAR-/- mice, pesticide-exposed CAR-/- males did not exhibit BW gain or changes in glucose metabolism compared to the CAR-/- males fed control chow. Moreover, CAR-/- females fed pesticide chow exhibited pesticide toxicity with higher BWs and mortality rate compared to the CAR-/- females fed control chow.ConclusionsTo our knowledge, we are the first to demonstrate a sexually dimorphic obesogenic and diabetogenic effect of chronic dietary exposure to a common mixture of pesticides at TDI levels, and to provide evidence for a partial role for CAR in an in vivo mouse model. This raises questions about the relevance of TDI for individual pesticides when present in a mixture. https://doi.org/10.1289/EHP2877.

Project description:BackgroundFor years the United States Department of Agriculture's Pesticide Data Program and the United Kingdom's Food Standards Agency have published annual or quarterly data on pesticide residues in foods. Both programs report residues in conventionally grown, organic, and imported foods. The US program has tested about 288,000 food samples since 1992, primarily fruits and vegetables consumed by children. Since 1999 the UK has tested about 72,000 samples of a wider range of foods. These data are vital inputs in tracking trends in pesticide dietary risks.MethodsThe Dietary Risk Index (DRI) system facilitates detailed analyses of US and UK pesticide residue data, trends, and chronic risk distributions. The DRI value for a pesticide is the dietary intake of that pesticide from a single serving of food divided by the pesticide's acceptable daily intake as set by the US Environmental Protection Agency. It can be calculated based on average annual residue concentrations, and on residue levels in individual samples of food. DRI values can be aggregated over multiple pesticides in single foods, and over individual pesticides in multiple foods.ResultsThe DRI system provides insights into the levels, trends, and distribution of pesticide dietary risk across most widely consumed foods. By drawing on both US Pesticide Data Program and UK-Food Standards Agency residue data, the DRI is capable of assessing pesticide risks in a significant portion of the global food supply. Substantial reductions in pesticide dietary risks occurred in the early 2000s, primarily from replacement of organophosphate insecticides with seemingly lower-risk neonicotinoids. However, there remain several areas of concern and opportunities to reduce risks. Both herbicide and fungicide dietary risks are rising. Organically grown produce poses risks far lower than corresponding, conventionally grown produce. Risk differences are inconsistent between domestic and imported foods.ConclusionsThe surest ways to markedly reduce pesticide dietary risks are to shift relatively high-risk fruits and vegetables to organic production. For other foods, reducing reliance on pesticides overall, and especially high-risk pesticides, will incrementally lower risks. The DRI system can help focus such efforts and track progress in reducing pesticide dietary risk.

Dataset Information

Pre- and Postnatal Dietary Exposure to a Pesticide Cocktail Disrupts Ovarian Functions in 8-Week-Old Female Mice.

Publications

Pre- and Postnatal Dietary Exposure to a Pesticide Cocktail Disrupts Ovarian Functions in 8-Week-Old Female Mice.

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