Intrauterine and lactational exposure to environmental plastic waste: impact on male gonadal development

• Grant number: 24/03207-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date until: December 01, 2024
• End date until: September 30, 2026
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Mirella Franco Moreira
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The increasing production and use of plastics has raised concerns due to the associated environmental and health impacts. In the environment, plastics are degraded into micro- and nanoplastics (MNPS), particles small enough to penetrate the human body through breathing, ingestion of water, contaminated food and even through the skin. Furthermore, phthalates, chemical agents used to manufacture flexible plastics, are ubiquitous in the environment due to their easy release during the degradation of these polymers, which can deregulate cellular pathways of endocrine control and interfere with hormonal homeostasis, impacting growth, development and in playback. Exposure to these compounds during development, especially in the DOHaD context, can have consequences for the adult life of the offspring. The testicle is of great importance for male reproductive development, production of sex hormones and fertility. However, studies suggest that phthalates are toxic to this organ, as they interfere with the androgenic and estrogenic regulation of gonadal development, potentially causing adverse effects on development and reproductive function in males. Thus, this work aims to investigate the effects of maternal exposure to phthalates and nanoplastics (alone and together) during pregnancy and lactation on the testicular development of rat offspring, identifying possible structural and functional changes in steroidogenic pathways in the fetus (gonadal and sexual differentiation ) and in pre-pubertal individuals (especially those related to Sertoli and Leydig cells), in oxidative balance and reproductive efficiency. 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 MG + 1mg/kg/day NPs 100 nm; T5: 200mg/kg/day MF + 1mg/kg/day NPs 100 nm. Treatment will be carried out by gavage from gestational day 10 (GD10) to postnatal day 21 (DPN21). The male offspring will be monitored regarding the development of the external genitalia, and the age of preputial separation will be measured. On DG 20, DPN 22 and DPN 120, rats from each group will be anesthetized and the testes will be collected for histological (HE) and molecular analyzes (RT-qPCR). Molecular analyzes will be carried out to evaluate the gene expression of targets related to the development and maturation of Leydig and Sertoli cells, steroidogenic pathways, maintenance of the blood-testicular barrier and oxidative stress.