Phthalates and nanoplastics and female reproductive toxicology: neonatal mouse whole ovaries and antral follicles in vitro

• Grant number: 24/21926-3
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: June 01, 2025
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Patrick Vieira de Souza
• Supervisor: Jodi Flaws
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: University of Illinois at Urbana-Champaign, United States
• Associated to the scholarship: 24/01724-7 - Plastic waste and reproductive toxicology: in vivo and in silico approaches to female reproductive aspects, BP.MS

Abstract

The widespread production and pollution of plastics has been gaining attention due to the effects of plastics polution on the environment and human health. Once in the environment, plastic polymers degrade into small particles called micro or nanoplastics, which can reach humans and cause health consequences. Furthermore, plastic additives are released into the environment and attach to the hydrophobic surface of nanoplastics, causing bioaccumulation and biomagnification. These additives include phthalates, substances classified as endocrine disruptor chemicals (EDCs), which are ubiquitous nowadays. The ovary is responsible for reproduction and hormone secretion, and is known to be a target of phthalates and other EDCs. Early exposure to phthalates has already been described as capable of altering the ovarian health of offspring and nanoplastics are capable of accumulating in tissues as well as enhancing the effects of phthalates. However, we know little about the mechanisms by which phthalates and nanoplastics affect ovarian healthThus, the proposed studies are designed to evaluate the influence of a relevant mixture of phthalate metabolites and nanoplastics on the ovary. The experiments will use both cultured whole neonatal ovaries which contain immature follicles and tadult antral follicles so we can understand the effects of phthalates and nanoplastics on ovarian follicles at different stages of development. Neonatal ovaries (PND4) and adult antral follicles (PND40-50) from Sprague Dawley female rats will be cultured for 4 days and 48 or 96h, respectively. The ovarian tissues will be treated with dimethyl sulphoxide (DMSO; vehicle control), phthalate metabolite mixture - MM (0.1, 1, and 10 ug/ml), nanoplastics - NP - 100nm (5,25 and 75 ug/ml), or metabolite mixture+nanoplastic (MM +NP). The phthalate metabolite mixture was derived from epidemiological studies in women. Finally, the ovary and antral follicles will be subjected to measures of ovarian health, including gene expression analysis of cell cycle, apoptosis regulators, and enzymes related to steroidogenesis.