EFFECT OF RESVERATROL ON SERTOLI CELL PROLIFERATION

GORGA A; RINDONE GM; REGUEIRA M; PELLIZZARI EH; CAMBEROS MC; CIGORRAGA SB; RIERA MF; GALARDO MN; MERONI SB

JOURNAL OF CELLULAR BIOCHEMISTRY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2018 vol. 119 p. 10131 - 10142

0730-2312

Resveratrol (RSV), a polyphenolic compound largely found in red grape skins, has been used as a nutritional supplement since it exhibits beneficial health effects, such as anti-cancer, cardioprotective, anti-aging, and anti-inflammatory effects. Particularly, it has been shown that it participates in mechanisms involved in cell proliferation. Sirtuin 1 (SIRT1) is considered a well known RSV effector. Noteworthy, Sirt1 knockout (KO) animals are infertile. The aim of this study was firstly, to determine if RSV has any effect on Sertoli cell proliferation and secondly if 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 FSH-stimulated conditions. BrdU incorporation and the expression of Cyclin D1, Cyclin D2, Cyclin D3, Cyclin E1 and Cyclin E2 and of the Cip/Kip cell cycle inhibitors p21Cip and p27Kip were analyzed. RSV decreased BrdU incorporation and Cyclins D1, D2, E1 and E2 expression and increased p21Cip and p27Kip 40 mRNA levels. RSV also decreased FSH-stimulated BrdU incorporation and Cyclin D1 andD2 mRNA levels. The effect of RSV on cMyc was also analyzed. RSV treatment did not modify basal and FSH-stimulated cMyc expression, while 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 andby regulating cMYC transcriptional activity participates in the regulation of immature Sertoli cell proliferation.