Evaluation of the ability of coenzyme Q10 to counteract the effects upon meiosis and/or early embryogenesis of bisphenol A, dibutyl phthalate, 2-(thiocyanomethylthio)benzothiazole, permethrin, and N,N-diethyl-meta-toluamide in Caenorhabditis elegans

• Grant number: 16/23481-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): May 20, 2017
• Effective date (End): May 19, 2018
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Fernando Barbosa Júnior
• Grantee: Maria Fernanda Hornos Carneiro
• Supervisor: Monica Paola Colaiacovo
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Harvard University, Boston, United States
• Associated to the scholarship: 16/07661-0 - Comparison of the toxicity of bisphenol A and bisphenol S individually and in association in HepG2 cells, BP.PD

Abstract

Endocrine disruptors can mimic natural hormones on their respective receptors leading to adverse effects. Caenorhabditis elegans (C. elegans) is a small nematode which has many instances of conservation of mode of toxic action in comparison to mammals. Preliminary studies of Dr Colaiacovo's group have identified 5 environmental chemicals: bisphenol A (BPA) and dibutyl phthalate (DBP), likely endocrine disruptors frequently used as plasticizers, as well as the pesticides 2-thiocyanomethylthio) benzothiazole (TCMTB), Permethrin, and N,N-diethyl-meta-toluamide (DEET), that result in increased chromosome non-disjunction and meiotic defects in C. elegans. Given the widespread prevalence of endocrine disruptors and pesticides in our environment, it is critically important to understand their impact on reproductive health and identify ways to mitigate their effects and improve fertility and early embryogenesis outcomes. Coenzyme Q10 (CoQ10) has been suggested to improve fertility outcomes, but overall data is still inconclusive. The aim of the study is to determine how BPA, TCMTB, Permethrin, DEET and DBP affect meiosis and/or early embryogenesis and whether CoQ10 can improve reproductive health outcomes. Brood size and embryonic viability of C. elegans will be examined following either continuous exposure to each of these five chemicals starting at eggs or 24- and 42-hour exposures starting at the L4 larval stage. This will be compared to vehicle and CoQ10 alone, to co-exposures (chemical + CoQ10) as well as to chemical exposures for worms starting as eggs followed by CoQ10 exposure starting at the L4 stage. Once a regimen is established that reproducibly exhibits the strongest improvements to embryonic lethality and/or sterility, we will follow strategies described below to examine whether there is an improvement of defects in chromosome morphology and synapsis, double-strand break repair, and increased germ cell apoptosis by using different techniques such as high-resolution microscopy, Fluorescence in situ Hybridization (FISH), RT-PCR, immunostaining, and RNA interference (RNAi).

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HORNOS CARNEIRO, MARIA FERNANDA; SHIN, NARA; KARTHIKRAJ, RAJENDIRAN; BARBOSA, JR., FERNANDO; KANNAN, KURUNTHACHALAM; COLAIACOVO, MONICA P.. Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline. Genetics, v. 214, n. 2, p. 381-395, FEB 2020. (16/23481-2)