Repercussions of maternal exposure to nanoplastics and phthalates: maternal aspects and susceptibility to prostatic oncogenesis in rats

• Grant number: 22/12304-3
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2023
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Wellerson Rodrigo Scarano
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Glaura Scantamburlo Alves Fernandes ; Jodi Flaws ; Josias Rodrigues
• Associated scholarship(s): 24/22078-6 - Impact of exposure to plastic waste on functional and oncogenic targets in human prostate cells, BP.IC; 24/15101-1 - Late impacts of intrauterine and lactational exposure to environmental plastic waste on testicular development with emphasis on the blood-testicular barrier, BP.IC; 24/02800-9 - Animal maintenance, welfare and treatment in the controlled experimental environment, BP.TT

Abstract

The plastic problem is one of the biggest public health challenges on the planet. Research has shown that global plastic production was 400 million tons in 2015, and an estimated 12 billion tons of plastic waste is expected to be produced by 2050. When plastics enter the environment, they degrade to form microplastics (MPs) and nanoplastics (NPs) that enter the body through breathing, ingesting contaminated water and food, and skin. Phthalates are plastic additives, which are not covalently bound to the polymer, and so are easily released into the environment. The intrauterine microenvironment has been the target of important alterations due to the interference of environmental factors that can generate late consequences. Due to the extreme importance of the subject, and faced with unpublished data (attached) showing that perinatal exposure to a mixture of phthalates (MFs) increased by 40% the incidence of adenocarcinomas in situ in the prostate of senile rats, this project aims to: 1- investigate the proteomic profile of the ventral prostate (PV) of senile rats exposed to MFs at different concentrations, aiming to compare the data with results obtained for young and adult animals (previous study); 2- analyze the proteomic profile of the prostate of adult rats exposed in the perinatal period to MFs and NPs; 3- perform study of the intestinal microbiome of animals treated in the different groups; 4- perform chronic exposure test for "in vitro carcinogenesis", in immortalized normal human prostate PNT-2 cells, with exposure to MFs in monoester and to nanoplastics (NPs), to evaluate differentially expressed genes and miRNAs, selected from in vivo studies and from TCGA (The Cancer Genome Atlas). For the in vivo study, SD pregnant rats will be distributed into 5 experimental groups: G1: (control; vehicle); T1: 20µg/kg/day MF; T2: 200mg/kg/day MF; T3: NPs; T4: 20µg/kg/day MF + NPs; T5: 200mg/kg/day MF+ NPs. Treatment will be given by gavage from gestational day 10 (DG10) to postnatal day 21 (PND21). Polystyrene nanospheres of 50-80 nm at the concentration of 1.0 mg/kg will be used. For the in vitro study, cells will be exposed to MFs and NPs continuously for 15 and 30 passages. For proteomic analyses, samples will be analyzed by mass spectrometry (LC-Ms/Ms). For gene expression analyses, samples will be analyzed by RTq-PCR. The role of targets in biological processes, molecular functions and cellular components will be evaluated in silico, and interaction networks for differentially expressed targets will be constructed. The analysis of the fecal microbiome will be based on the analysis of polymerase chain reaction amplicon sequences from stool samples. Studies like this one can foster discussions about public policies related to the production, dispersion and reuse of plastic around the world. (AU)