Effect of resveratrol on Sertoli cell proliferation

Resveratrol (RSV), a polyphenolic compound largely found in red grape skin, has been used as a nutritional supplement as it exhibits beneficial health effects, such as anticancer, cardioprotective, antiaging, and anti-inflammatory. Particularly, it has been shown that it participates in the mechanisms involved in cell proliferation. Sirtuin 1 (SIRT1) is considered a well-known RSV effector. Noteworthy, Sirt1-knockout animals are infertile. The aim of this study was, first, to determine whether RSV has any effect on Sertoli cell proliferation and, second, whether SIRT1, a putative target of RSV, is present in immature Sertoli cells. Sertoli cell cultures obtained from 8-day-old rats, which actively proliferate, were treated with RSV (10 and 50 µM) under basal and follicle-stimulating hormone (FSH)-stimulated conditions. Bromodeoxyuridine (BrdU) incorporation and the expression of cyclins D1, D2, D3, E1, and E2 and the Cip/Kip cell cycle inhibitors p21^Cip and p27^Kip were analyzed. RSV decreased BrdU incorporation and cyclins D1, D2, E1, and E2 expression and increased p21^Cip and p27^Kip messenger RNA (mRNA) levels. RSV also decreased FSH-stimulated BrdU incorporation and cyclins D1 and D2 mRNA levels. The effect of RSV on cMYC was also analyzed. RSV treatment did not modify basal and FSH-stimulated cMyc expression; however, it inhibited basal and FSH-stimulated cMYC transcriptional activity, suggesting a role of cMYC in RSV effects. Additionally, Sirt1 was detected in immature Sertoli cells. Altogether, these results suggest that RSV possibly, by activating SIRT1 and regulating cMYC transcriptional activity, participates in the regulation of immature Sertoli cell proliferation.