Role of the resveratrol in reversing reproductive damage caused by nicotine in adult male rats, exposed during intrauterine phase and breast-feeding

• Grant number: 19/26648-3
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2020
• Effective date (End): October 31, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Sandra Maria Miraglia Valdeolivas
• Grantee: Camila Monteiro Francisco
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Nicotine is one of the most consumed legal drugs in the world through smoking. Both nicotine and its major metabolite, the cotinine, cross the hematoplacental membrane. High concentrations of these substances are observed both in pregnant women's blood plasma and in the breast milk of smokers. Nicotine causes reproductive changes that can lead to infertility and subfertility in men and women, as well as pregnancy and embryonic development disorders. One of the main mechanisms of action of nicotine on the body occurs by reducing oxidative stress. Resveratrol is a phytoalexin with several beneficial properties, namely: antioxidant, anti-inflammatory, antiapoptotic, anticancer, antiaging, among others. This research aims to investigate, using the rat as an experimental model, the capacity of resveratrol to reverse nicotine damage on reproduction of male rats exposed during the intrauterine and breast-feeding phases. For this scope, from male offspring obtained from rat dams exposed and not exposed to nicotine, 4 groups will be formed: Control "Sham" (S), Resveratrol (R), Nicotine (N), Nicotine Resveratrol (NR ). The females (sows) that will originate the N and NR group will be chronically treated throughout the gestation and lactation with the dose of 2 mg/kg/day of nicotine. Resveratrol will be administered by gavage (300 mg / kg body weight) to animals in groups R and NR for 63 days from the 51st day postpartum (dpp) to young adulthood based on the period total spermatogenesis and sperm transit time (53 days 10 days, respectively). Forty animals will be used, 10 per group. The animals will be euthanized at 114 dpp. At this age, male offspring will be evaluated for quantitative and qualitative sperm parameters and Sirtuin1 immunoexpression in the testes. SIRT1 is a deacetylase-type protein found in various germ cell types, acting positively on male reproduction due to its activity on chromatin condensation and thus, on sperm chromatin protamination. SIRT1 expression may be affected by nicotine action but, on the other hand, it is modulated by RES action, which may favor the reduction of reproductive damage caused by the toxicity of this important cigarette component. The possible reversal of this damage related to sperm parameters of adult rats exposed to nicotine during the intrauterine and breast-feeding phases will be investigated. (AU)