Consequences of maternal exposure to phthalates and nanoplastics on the sex-specific hypothalamic global proteomic profile of aging rats

• Grant number: 24/22188-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2025
• End date: November 30, 2028
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Matheus Naia Fioretto
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

global plastic production was 400 million tons in 2015, and according to estimates, 12 billion tons of plastic waste are expected to be produced by 2050. When plastics enter the environment, they degrade to form microplastics (MPs) and nanoplastics (NPs) that penetrate the body through respiration, ingestion of contaminated water and food, and skin. The intrauterine microenvironment has been subject to significant changes due to the interference of environmental factors that can generate immediate and delayed consequences, and can harm central organs with numerous functions, such as the hypothalamus. Therefore, the objective is to evaluate the effects of maternal exposure during pregnancy and lactation to a mixture of phthalates and NPs, isolated or combined, and their sex-specific consequences on the global hypothalamic proteomic profile during aging. For this purpose, pregnant Sprague Dawley rats were be distributed into 6 groups: C: (control; vehicle); T1: 20µg/kg/day of the phthalate mixture (MF); T2: 200mg/kg/day MF; T3: 1mg/kg/day of 100 nm nanoplastics (NPs); T4: 20µg/kg/day MF + 1mg/kg/day 100 nm NPs; T5: 200mg/kg/day MF + 1mg/kg/day 100 nm NPs. Treatment was be administered orally from gestational day to postnatal day (PND21). Subsequently, the rats were maintained until PND540 without any further exposure. After euthanasia, we will perform a global proteomic profile of the hypothalamus, assess differentially expressed proteins, create a MicroRNOMA, and perform morphological and molecular validations (rtqPCR and Western Blotting). For functional analyses, cells (SH-SY5Y Cell Line human - neuroblast from nervous tissue) will be cultured in the following groups: Control (CT): culture medium + DMSO (at the same concentration used in the treatments); Treatment 1: culture medium + phthalate mixture; Treatment 2: culture medium + nanoparticles; Treatment 3: culture medium + mixture + nanoparticles. Thus, the expected results are that there will be isolated adversities and the mixture of phthalates and NPs, influencing sex-specific differences in distinct regions of the hypothalamus of the animals during aging, which may provide biomarkers that are correlated with the potential risk for the development of chronic noncommunicable diseases, as well as identify specific regions that are affected by such conditions. (AU)