Gestational exposure to glyphosate-based herbicide and glucose homeostasis in rats: effects on dams during pregnancy and post-term periods, and on their progeny
Documento
Informações
Título
Gestational exposure to glyphosate-based herbicide and glucose homeostasis in rats: effects on dams during pregnancy and post-term periods, and on their progeny
Título (EN)
Gestational exposure to glyphosate-based herbicide and glucose homeostasis in rats: effects on dams during pregnancy and post-term periods, and on their progeny.
Autor(es)
Aline Barbosa Lima 1, Victoria Cristina Malinski 2, Morgana Contini 3, Natália Stinghen Tonet 4, Bianca Franco Leonardi 5, Rodrigo Augusto Foganholi da Silva 6, Willian T Festuccia 5, Ivan Quesada 7, Alex Rafacho 8 | 1Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Graduate Program in Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil. 2Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil. 3Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil. 4Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Graduate Program in Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil. 5Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-000, Brazil. 6Center of Epigenetic Study and Gene Regulation - CEEpiRG, Program in Environmental and Experimental Pathology, Paulista University - UNIP, São Paulo, Brazil. 7Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernandez, Elche, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Spain. 8Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Graduate Program in Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Graduate Program in Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Developmental Origins of Health and Disease National Institute of Science, Technology and Innovation (INCT DOHaD Brasil), Maringá, Brazil. Electronic address: alex.rafacho@ufsc.br.
Instituição
Universidade Paulista
Tipo
Manuscrito
Tipo de Mídia
Jornal
Resumo (EN)
Exposure to glyphosate-based herbicides (GBH) may affect metabolism and induce endocrine alterations. This study evaluated whether environmentally relevant low doses of GBH affect glucose homeostasis during pregnancy and the metabolism of offspring later in life. Pregnant Wistar rats received daily oral doses of either 0.5 or 50 mg/kg of GBH or water (control) throughout the gestation period. No significant changes were observed in biometric and metabolic parameters during pregnancy. However, hepatic alterations were detected in GBH-treated rats, including reduced glycogen content and decreased global genome methylation. Offspring exhibited a transient delay in neurodevelopmental reflexes. Body mass and food intake remained unchanged up to postnatal day 70. After this period, animals were subjected to a metabolic challenge with dexamethasone. While dexamethasone-treated animals showed metabolic alterations typical of glucocorticoid exposure (glucose intolerance, insulin insensitivity, dyslipidemia), maternal GBH exposure during pregnancy did not exacerbate these effects in the offspring. Additionally, changes in DNA methylation-related gene expression were observed in female but not male offspring. In vitro, GBH exhibited greater cytotoxicity than glyphosate alone, significantly reducing the viability of 3T3-L1 adipocytes and HepG2 hepatocytes, whereas glyphosate alone had no significant effects, even at higher concentrations. Overall, gestational exposure to GBH under regulatory safe doses does not cause substantial metabolic disturbances in dams or their offspring. However, the existence of alterations in hepatic glucose metabolism and effects on hepatic epigenetic regulation at these low doses, along with the cytotoxic in vitro effects of GBH at high concentrations, warrants attention regarding human exposure and health impacts.
Resumo
A exposição a herbicidas à base de glifosato (GBH) pode afetar o metabolismo e induzir alterações endócrinas. Este estudo avaliou se baixas doses de GBH, ambientalmente relevantes, afetam a homeostase da glicose durante a gestação e o metabolismo da prole posteriormente. Ratas Wistar prenhes receberam doses orais diárias de 0,5 ou 50 mg/kg de GBH ou água (controle) durante todo o período gestacional. Não foram observadas alterações significativas nos parâmetros biométricos e metabólicos durante a gestação. No entanto, foram detectadas alterações hepáticas nas ratas tratadas com GBH, incluindo redução do conteúdo de glicogênio e diminuição da metilação global do genoma. A prole apresentou um atraso transitório nos reflexos do desenvolvimento neurológico. A massa corporal e a ingestão alimentar permaneceram inalteradas até o 70º dia pós-natal. Após esse período, os animais foram submetidos a um desafio metabólico com dexametasona. Embora os animais tratados com dexametasona tenham apresentado alterações metabólicas típicas da exposição a glicocorticoides (intolerância à glicose, resistência à insulina, dislipidemia), a exposição materna ao GBH durante a gestação não exacerbou esses efeitos na prole. Adicionalmente, foram observadas alterações na expressão gênica relacionada à metilação do DNA em filhotes fêmeas, mas não em machos. In vitro , o GBH exibiu maior citotoxicidade do que o glifosato isoladamente, reduzindo significativamente a viabilidade de adipócitos 3T3-L1 e hepatócitos HepG2, enquanto o glifosato isoladamente não apresentou efeitos significativos, mesmo em concentrações mais elevadas. De modo geral, a exposição gestacional ao GBH em doses seguras regulamentares não causa distúrbios metabólicos substanciais em fêmeas ou em seus filhotes. Contudo, a existência de alterações no metabolismo hepático da glicose e efeitos na regulação epigenética hepática nessas baixas doses, juntamente com os efeitos citotóxicos in vitro do GBH em altas concentrações, justifica atenção quanto à exposição humana e seus impactos na saúde.
Palavras-chave
Endocrine alterations; Glucose homeostasis; Glyphosate; Herbicides; Neurodevelopment; Pregnancy; RoundUp.
Publicado em
LIMA, Aline Barbosa; MALINSKI, Victoria Cristina; CONTINI, Morgana; TONET, Natália Stinghen; LEONARDI, Bianca Franco; SILVA, Rodrigo Augusto Foganholi da; FESTUCCIA, Willian T.; QUESADA, Ivan; RAFACHO, Alex. Gestational exposure to glyphosate-based herbicide and glucose homeostasis in rats: effects on dams during pregnancy and post-term periods, and on their progeny. Environmental Pollution, v. 397, art. 127942, 2026.
Direito de Acesso
Acesso Aberto
Financiamento
Vice-Reitoria de Pós-Graduação e Pesquisa - Universidade Paulista