Population control of synanthropic animals: morphological, functional and biochemical aspects of the contraception promoted by new routes of administration of ethane dimethanesulfonate to male Wistar rats

• Grant number: 21/09882-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2021
• End date: March 31, 2024
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Wilma de Grava Kempinas
• Grantee: Jorge Willian Franco de Barros
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant(s): 24/05711-7 - 1st Workshop on wildlife fertility control: what now? what next? where to?, AR.EXT
• Associated scholarship(s): 22/16531-4 - Interactions of ethane dimethanesulfonate (EDS) with the leydig cell lines R2C, MA-10, and MLTC-1: an in vitro approach to understand the molecular mechanism of EDS action, BE.EP.DR

Abstract

The overpopulation of synanthropic and stray animals creates a chaotic scenario for the application of effective population control strategies. These animals, including rodents, circulate freely in urban centers, reproduce, in addition to contributing to the transmission of zoonotic pathogens and causing accidents. Surgical contraceptive methods in these cases are unfeasible, leading to practices of non-humanized techniques, which include euthanasia, poisoning, and baits, contributing to animal suffering, as well as environmental and ecological imbalances. In this context, our Laboratory, in collaboration with Dr. Gary Klinefelter (US EPA) has shown promising anti-fertility results in laboratory rats, after oral administration of ethane dimethanesulfonate (EDS), an agent with known selective cytotoxicity on Leydig cells after gavage and intraperitoneal injections. As a follow up of these studies, supported by FAPESP, the present project aims to evaluate morphofunctional, biochemical, and contraceptive aspects of infertility promoted by EDS, in male Wistar rats, using alternative routes of chemical administration. The doses and additional details of experimental design are omitted due to patent application (AUIN/Unesp Code 18CI097). Adult male Wistar rats (90 days of age; n = 10 / group) will be exposed to EDS via intratesticular injections (uni or bilateral injections with EDS) or intrascrotal implant (Silastic tube filled with EDS). Control groups will be subjected to the same treatment but will receive only the vehicle. Additional groups (n = 10 / group) treated with EDS via intraperitoneal or oral administration (gavage) will serve as positive controls for both experiments. The animals will be evaluated in two different periods, 4 and 10 weeks after exposures, associated with the spermatogenesis and sperm transit time through the epididymis in rats. Copulatory behavior, fertility, sperm quality and quantity, testicular and epididymal histophysiology, serum hormonal concentrations, and biomarkers of toxicity in the liver and kidney will be evaluated. Additional parameters will be assessed, depending on the concession of a BEPE scholarship, allowing further international collaboration. Thus, our goal is, from this study with rodents, to evaluate the feasibility of using EDS, administered through different routes, as a candidate for a safe, humanized, rapid and effective compound with anti-fertility effects in other synanthropic, stray, pet, zoo and farmed species.