Influence of perinatal exposure to plasticizers on hypothalamic parameters of sexual differentiation

• Grant number: 24/08320-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Victória Cristina Pinha
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The intrauterine microenvironment has been the target of significant changes due to interference from environmental and/or socio-economic factors, which can have late consequences. The problem of plastic is one of the biggest public health challenges on the planet. Research has shown that global plastic production amounted to 400 million tons in 2015, and according to estimates, 12 billion tons of plastic waste will 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 through the skin. Phthalates are additives that give plastic malleability, do not bind covalently to the polymer and are therefore easily released into the environment. Phthalates are classified as endocrine disruptors (EDs) and have been detected in different proportions and concentrations in breast milk, the urine of pregnant women, amniotic fluid and the placenta of humans and rodents. Due to the extreme importance of the subject, the study seeks to analyze the histological aspects and gene expression of the hypothalamus of DPN22 rats exposed in the gestational and lactational periods to a mixture of phthalate diesters (MFs) and NPs, in order to investigate changes in hypothalamic sexual differentiation pathways. For the study, pregnant rats of the Sprague Dawley strain 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 phthalate mixture was based on a study that determined the proportion of different phthalates in the urine of pregnant women, and the doses were based on the dose of environmental exposure. In addition, 100 nm polystyrene nanospheres will be used at a concentration of 1.0 mg/kg/day. Treatment will be given orally from gestational day 10 (GD10) to postnatal day 21 (PND21). On PND22, the males' blood will be collected for hormone dosages, the hypothalamus will be collected for histological analysis (light microscopy and immunohistochemistry) and gene expression analysis by RTq-PCR for KiSS-1 and GPR54 (responsible for regulating reproductive function) NR5A1; (development and function of the HHG axis); GnRH (release of hormones), AR (androgen receptor); CYP19 (responsible for converting androgenic hormones into estrogen); SRD5A2 (conversion of testosterone into dihydrotestosterone).