Effects of maternal exposure to plastic waste from a DOHaD perspective: influence of environmental stressors on the prostate of rats

Abstract

The intrauterine microenvironment has been subject to important changes due to the interference of environmental and/or socioeconomic factors, which can generate late consequences. 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 according to estimates, 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, ingestion of contaminated water and food, and through the skin. Phthalates are plastic additives that are not covalently linked to the polymer and are therefore easily released into the environment. Phthalates represent a class of molecules detected in different proportions and concentrations in breast milk, pregnant women's urine, amniotic fluid and human and rodent placenta. Due to the extreme importance of the subject, the study seeks to analyze the histopathological and molecular aspects in the ventral prostate of rats in DPN120 exposed in the perinatal period to a mixture of phthaltate diesters (MFs) and NPs, in order to investigate changes in the organ. For the study, pregnant Sprague Dawley rats will be distributed into 4 experimental groups: Ctrl: (control; vehicle); T1: 20µg/kg/day MF; T2: NPs; T3: 20µg/kg/day MF + NPs. The proportion of the mixture was based on a study that determined the amount of different phthalates in the urine of pregnant women, and the doses were based on the dose of environmental exposure. 100 nm polystyrene nanospheres will be used at a concentration of 1.0 mg/kg/day. Treatment will be carried out by gavage from gestational day 10 (GD10) to postnatal day 21 (DPN21). In DPN120, the males' blood will be collected for hormonal measurements, the ventral prostates will be collected for histopathological and cytochemical analyses; immunohistochemistry and validation of differentially expressed targets from a proteomic analysis carried out with the same experimental design in our research group, through gene expression analyzes (RTq-PCR) or protein analysis (Western Blotting) with a focus on functional and oncogenic targets .