Plastic waste and reproductive toxicology: in vivo and in silico approaches to female reproductive aspects

• Grant number: 24/01724-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Patrick Vieira de Souza
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 24/21926-3 - Phthalates and nanoplastics and female reproductive toxicology: neonatal mouse whole ovaries and antral follicles in vitro, BE.EP.MS

Abstract

One of the biggest current problems linked to human activity and the environment is exposure to environmental contaminants such as plastics and their additives. In this context, among the most studied and ubiquitous substances used in the manufacture of plastics and easily leached into the environment are phthalates. Additionally, micro/nanoplastics (MNP) have been gaining attention in scientific circles due to the increase and dispersion of these microparticles in different environments and their harmful properties to human health. Inserted in this context, the concept of the Developmental Origin of Health and Disease (DOHaD) postulates that the intrauterine and perinatal environment is decisive for the development of offspring, and that exposure to stressors can increase susceptibility to diseases throughout life. In the midst of this problem, the development of the genital system, especially the female one, has an impact that may be related not only to female fertility, but also to changes that can be transmitted through generations. Linked to the DOHaD concept, maternal exposure to plastic and nanoplastic additives can impact the development and modulation of the ovarian epigenome, leading to reproductive, hormonal and pathological changes. Therefore, the objective of this work is to evaluate the effects of exposure to nanoplastics and phthalates during pregnancy/lactation on parameters of reproductive maturity, ovarian development and maturation, as well as on the proteomic profile of the female gonad in the offspring of exposed mothers. For this, pregnant SD rats will 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 NPs 100 nm; T5: 200mg/kg/day MF + 1mg/kg/day NPs 100 nm. Treatment will be administered orally from gestational day 10 (GD10) to postnatal day (DPN21), based on previous studies. The female offspring will be monitored for vaginal opening, first estrus and estrous cyclicity. On DPN22 and 120, rats from each group will be anesthetized and the ovaries will be collected for histological analysis (HE) and evaluation of the follicles and for proteomic analysis. Furthermore, the proteomics results will be analyzed in silico and the main targets will be validated by western blotting. Targets related to endocrine reproductive changes and oncogenic pathways will be the main targets for large-scale analyses.