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Neonatal Exposure to Di-(2-Ethylhexyl) Phthalate (Dehp) Through Breastfeeding Leads to Dysfunction endocrine-metabolic Outcomes in Male Rats at Adulthood: An in Vivo and in Silico Approach

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SSRN 2025年

作者： Santos-Silva, Ana Paula Macario, Thayná M. Melo Santos, Anne R. Barbosa, Yuri Vieira Miranda-Alves, Leandro UFRJ Multidisciplinary Research Center - Xerém in Biological Sciences Brazil - NUMPEX-BIO Campus Duque de Caxias Professor Geraldo Cidade Federal University of Rio de Janeiro Brazil Federal University of Rio de Janeiro Xerem Campus Brazil Research Group on Endocrine Disruptors and Metabolic Programming Laboratory of Endocrinology and Energy Metabolism Prof. João Paulo Gabriel Camporez School of Medicine University of São Paulo Brazil Laboratory of Experimental Endocrinology - LEEx Institute of Biomedical Sciences Federal University of Rio de Janeiro Brazil

Stimuli to which the individual is exposed can influence the phenotype of the adult when they occur in phases of greater susceptibility, as defined by the DOHaD concept, developmental origin of health and disease. endocrine disruptors (EDs) are natural and/or synthetic molecules that have the ability to influence the role of hormones, among which phthalates stand out. Obesity is a chronic, multifactorial disease, with an increase in prevalence in the population in recent years, and exposure to EDs may have an influence on this scenario. Given this, we propose to verify whether the presence of DEHP (di-2- etilhexil phtalate), in the critical phases as lactation, could influence the metabolism in adult life. Lactating Wistar rats were kept with 6 male pups and divided at groups of 100 mg/kg/day, 500 mg/kg/day, and sesame oil (control) that occurred from postnatal days (PN1D) to PND21, when half of the offspring were euthanized and the other half maintained until adulthood (PND90). In PND21, the 500DEHP group showed a decrease in weight and visceral adiposity, increase in insulin and serum T3 levels. Adult animals had an increase in visceral adiposity for the 500DEHP group, with increased cumulative food intake, reduction in serum leptin and increased serum T3 levels. In silico interation between DEHP and AS160 protein suggesting potencial mechanism of action for DEHP. This data set suggests that DEHP has the potential to influence the development of the offspring, when exposure occurs exclusively during the lactation period, with metabolic consequences associated with obesity at long-term. © 2025, The Authors. All rights reserved.

关键词： Nutrition

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