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Sirtuin 1 (SIRT1) protein can positively act on male reproduction, and its expression can be affected by nicotine and modulated by resveratrol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The capability of resveratrol to reverse the reproductive damage in adult male offspring, which was nicotine\u2010exposed during the intrauterine phase and breastfeeding, was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Four groups were established with male offspring born from nicotine\u2010exposed and non\u2010exposed rat dams during pregnancy and lactation. Forty\u2010eight male Wistar rats were distributed into four groups: sham control (SC), resveratrol (R), nicotine (N), and nicotine + resveratrol (NR). Rat dams of the N and NR offspring were exposed to nicotine (2\u00a0mg\/kg\/day) during pregnancy and lactation using a subcutaneously implanted minipump. The offspring of the R and NR groups received resveratrol (300\u00a0mg\/kg of body weight, gavage) for 63 days from puberty. At 114 days of age, the male rats were euthanized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nicotine did not alter the body weight, biometry of reproductive organs, or quantitative sperm parameters of adult offspring but caused an evident worsening of all sperm qualitative parameters studied. Daily treatment with resveratrol from puberty up to adulthood improved all qualitative sperm parameters significantly, leading some of them close to the control values. Resveratrol also improved the morphological integrity and expression of SIRT1 in the seminiferous epithelium of nicotine\u2010exposed offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Discussion<\/jats:title><jats:p>Resveratrol reversed the male reproductive damage caused by nicotine. Nicotine crosses the blood\u2010placental membrane and is present in the breast milk of mothers who smoke. Resveratrol restored the altered reproductive parameters in the male adult offspring that were nicotine\u2010exposed during intrauterine life and breastfeeding. The epigenetic modulating action of resveratrol can be involved in this nicotine damage reversion. Resveratrol may be a promising candidate to be investigated regarding the adjuvant strategies in the treatment of male infertility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13183","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T16:17:11Z","timestamp":1650989831000},"page":"951-972","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Resveratrol reverses male reproductive damage in rats exposed to nicotine during the intrauterine phase and breastfeeding"],"prefix":"10.1111","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-7978","authenticated-orcid":false,"given":"Camila Monteiro","family":"Francisco","sequence":"first","affiliation":[{"name":"Department of Morphology and Genetics Federal University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo 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