Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms

Phytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinetic properties. The study aimed to assess the impact of vaginal R-HA gel on the reproductive system in ovariectomized rats. Methods: The study was carried out on Wistar female rats. It investigated the body weight, tail temperature, vaginal pH, estrogen and progesterone blood levels, and immunohistochemical biomarkers (COX2, Casp-3, Bcl-2, and VEGF). Animals were divided into control animals; ovariectomized rats (OVX); and OVX group treated with vaginal 0.5% R-HA gel (0.5%, 0.1 mL, daily 28 days). Results: The R-HA gel’s therapeutic effect was manifested by slowing weight gain by 17% (p < 0.001), less pronounced symptom of fever at the root of the tail by 9% (p < 0.001) and lowering the vaginal pH to 4.4–4.5 compared with OVX rats. The anti-inflammatory effect and the reduction of COX-2 expression in vagina were accompanied by antiapoptotic impact of RA-H on endometrium, associated with the decreased Casp-3 expression (p < 0.001) and elevated Bcl-2 score in endometrial glands (p = 0.01). Together with enhanced VEGF expression in endometrial glands (p < 0.001) and stromal cells (p = 0.007), these changes prevented endometrial atrophy (p < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders.