Perinatal exposure to a glyphosate pesticide formulation induces offspring liver damage

Rieg, Carla Elise Heinz; Cattani, Daiane; Naspolini, Nathalia Ferrazzo; Cenci, Vitoria Hayduck; Cavalli, Vera Lúcia de Liz Oliveira; Jacques, Amanda Virtuoso; Nascimento, Marcus Vinícius Pereira dos Santos; Dalmarco, Eduardo Monguilhott; Moraes, Ana Carolina Rabello de; Santos-Silva, Maria Cláudia; Silva, Fátima Regina Mena Barreto; Parisotto, Eduardo Benedetti; Zamoner, Ariane

doi:10.1016/j.taap.2022.116245

Cited by 15 publications

(7 citation statements)

References 66 publications

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“…Hence, manipulation of IL-6 activity could benefit individuals with MDD and inflammatory characteristics [ 36 ]. Perinatal exposure to Gly significantly increased IL6 expression and caused liver damage in rat offspring [ 31 ]. In addition, Gly induced an inflammatory response mediated by elevated IL6 and altered the microbial composition in the rat intestine [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Clarification of the molecular mechanisms underlying glyphosate-induced major depressive disorder: a network toxicology approach

Li,

2024

Ann Gen Psychiatry

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Major depressive disorder (MDD) is predicted to become the second most common cause of disability in the near future. Exposure to glyphosate (Gly)-based herbicides has been linked to the onset of MDD. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the potential molecular mechanisms of MDD induced by Gly using network toxicology approach. The MDD dataset GSE76826 from the Gene Expression Omnibus database was referenced to identify differentially expressed genes (DEGs) in peripheral blood leukocytes of MDD patients and controls. The potential intersection targets of Gly-induced MDD were screened by network toxicology. The intersection targets were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and to construct protein–protein interaction networks. The binding potentials of hub targets with Gly were validated by molecular docking. In total, 1216 DEGs associated with Gly-induced MDD were identified. Subsequent network pharmacology further refined the search to 43 targets. GO and KEGG enrichment analyses revealed multiple signaling pathways involved in GLY-induced MDD. Six potential core targets (CD40, FOXO3, FOS, IL6, TP53, and VEGFA) were identified. Finally, molecular docking demonstrated that Gly exhibited strong binding affinity to the core targets. The results of this study identified potential molecular mechanisms underlying Gly induced MDD and provided new insights for prevention and treatment.

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Section: Discussionmentioning

confidence: 99%

Clarification of the molecular mechanisms underlying glyphosate-induced major depressive disorder: a network toxicology approach

Li,

2024

Ann Gen Psychiatry

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“…While some studies have shown that organic food consumption during pregnancy is associated with better nutritional status, others have shown no significant dif- ferences (Vigar et al, n.d.). However, there have been multiple studies that showed that glyphosate exposure may lead to adverse pregnancy outcomes, such as preterm-birth, smaller newborns, and congenital anomalies (Rull, Ritz, and Shaw 2006;Parvez, Gerona, Proctor, et al, n.d.;Brantsaeter, Torjusen, Meltzer, et al 2016;Rieg, Cattani, Naspolini, et al 2022;Gerona, Reiter, Zakharevich, et al 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Glyphosate is the active ingredient in many commonly used commercial and agriculture herbicides (Brantsaeter, Torjusen, Meltzer, et al 2016). Significant animal and human research has suggested that herbicides cross the placenta and may increase the risk of certain diseases later in life, such as cancer and neurodevelopmental disorders (Baudry, Assmann, Touvier, et al 2018;Carmichael et al 2007;Rieg, Cattani, Naspolini, et al 2022;Bradman et al 2003;Bossi et al 2013).…”

Section: Introductionmentioning

confidence: 99%

A latent class analysis of dietary intake in a midwestern United States pregnancy cohort

Jampa,

Moss,

Flannery

et al. 2024

North American Proceedings in Gynecology &Amp; Obstetrics

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Objective To use dietary self-reported data in a United States Midwest pregnancy cohort to characterize patterns of food consumption in pregnancy. Methods Using a Midwest US pregnancy cohort, a self-reported food questionnaire completed in pregnancy characterized food consumed within the last week. The 89 different foods in 14 categories were analyzed, as well as the percentage of each food that was consumed that was organic. Using a latent class analysis, individuals were assigned to classes based on healthy and organic food reported. Sociodemographic characteristics were compared between the classes. Results The 359 participants completing surveys were placed into 3 classes: I (healthy diet, higher organic, 23.4%)), II (healthy diet, lower organic, 42.6%), and III (less healthy diet, 34.0%). Individuals in each class demonstrated significant differences in multiple demographic and socioeconomic characteristics including race, age, marital status, educational attainment, income, smoking, and alcohol consumption. Conclusion A latent class analysis of self-reported dietary consumption yielded 3 classes that can be utilized in analyses of herbicide concentrations and adverse pregnancy outcomes. They may also serve as a screening aid in helping providers with dietary recommendations or interventions to optimize pregnancy outcomes.

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“…Previous studies have demonstrated links between ovarian dysfunction and non-alcoholic fatty liver disease ( Macut et al , 2017 ; Paschos and Paletas, 2009 ; Vassilatou, 2014 ). Additionally, GD 5 to PND 15 exposure to GBH impacted several hepatic parameters including increased inflammation markers in rats ( Rieg et al , 2022 ) and in adult mice ( Gomes et al , 2022 ). A greater number of hepatic than ovarian proteins were altered in female offspring.…”

Section: Discussionmentioning

confidence: 99%

“…Maternal exposure to GLY or GBH has reported impacts on cardiac parameters ( de Marins et al , 2023 ), anxiety and hyperactivity ( de Castro Vieira Carneiro et al , 2023 ), immune responsivity ( Buchenauer et al , 2022 ), hepatic function ( Rieg et al , 2022 ; Teleken et al , 2020 ), and muscle structure ( Barbosa et al , 2022 ) in offspring and although the species and route of exposure differ, the potential for maternal exposure to impair offspring viability is supported. This study investigated a maternal pre-conceptional exposure to GLY at a dose not previously determined to be of concern for development and reproduction ( Ganesan and Keating, 2020 ; Ganesan et al , 2020 ; USEPA, 1993 ).…”

Section: Discussionmentioning

confidence: 99%

Maternal pre-conceptional glyphosate exposure impacts the offspring hepatic and ovarian proteome

Novbatova

Timme

Severin

et al. 2023

Toxicological Sciences

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Glyphosate (GLY) is an herbicide used for rural and urban weed control. Urinary GLY in women is associated with shortened gestational length yet effects of GLY on offspring due to maternal exposure are unclear. This study tested the hypothesis that maternal chronic pre-conceptional GLY exposure would cause phenotypic and molecular changes in F1 offspring. Female C57BL/6 mice (7 wk old; n = 40) received saline vehicle control (CT; n = 20) or GLY (2 mg/Kg; n = 20) daily per os for ten weeks. At dosing completion, females were housed with unexposed males and divided into Cohort 1 who were euthanized at gestation day (GD) 14 (n = 10 per treatment), and Cohort 2 who completed gestation (n = 10 per treatment). F1 female ovarian and liver samples underwent LC-MS/MS and bioinformatic analysis. Maternal exposure did not affect litter (P > 0.05) sex ratio, or embryonic or neonatal gross phenotypes. In Cohort 2 offspring, no treatment effect on (P > 0.05) offspring anogenital distance, puberty onset or ovarian follicular composition was noted. Body weight was increased (P < 0.05) in male GLY-exposed compared to CT dam offspring. F1 females from GLY-exposed dams, had altered (P < 0.05) abundance of 54 ovarian and 110 hepatic proteins. Pathways altered in the ovary (FDR ≤ 0.07) included thermogenesis and PI3K-AKT signaling and in liver (FDR ≤ 0.08) included metabolic, glutathione metabolism, oxidative phosphorylation, non-alcoholic fatty liver disease, and thermogenesis. Thus, pre-conceptional GLY exposure affected offspring phenotypic and molecular profiles potentially impacting reproductive health.

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Perinatal exposure to a glyphosate pesticide formulation induces offspring liver damage

Cited by 15 publications

References 66 publications

Clarification of the molecular mechanisms underlying glyphosate-induced major depressive disorder: a network toxicology approach

Clarification of the molecular mechanisms underlying glyphosate-induced major depressive disorder: a network toxicology approach

A latent class analysis of dietary intake in a midwestern United States pregnancy cohort

Maternal pre-conceptional glyphosate exposure impacts the offspring hepatic and ovarian proteome

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