(176) Resveratrol enhances fertility by promoting the endometrial mitochondrial functions in cows

Ibuki Matsufuji¹, Satoru Kato², Sho Nakamura¹, Satoshi Ohkura¹, Koji Kimura³, Shuichi Matysyama¹

1. Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Aichi, Japan

2. Gunma Prefecture Livestock Experiment Station, Gunma, Japan

3. Laboratory of Reproductive Physiology, Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan

Abstract Text:

We previously revealed that mitochondrial dysfunction in the endometrial cells is a cause of decreased fertility in cows. Resveratrol, a small polyphenolic compound, exerts antioxidant effects. It activates sirtuin (SIRT)-1, enhancing mitochondrial biogenesis in the liver and mitochondrial activity in the muscles of mice. It also increases the SIRT1 expression, ATP content, mitochondrial membrane potential, and fertilization capacity of bovine oocytes. However, its specific effects on endometrial mitochondrial functions remain unclear. In this study, we hypothesized that resveratrol increases fertility by promoting the endometrial mitochondrial functions in cows. To verify this, we examined the effects of resveratrol on mitochondrial functions using bovine endometrial cells in vitro. Bovine endometrial cells (epithelial cells: n = 6; stromal cells: n = 6) were incubated with resveratrol (0, 10, and 50 µM). The gene expressions of SIRT1, mitochondrial fission 1 (FIS1), mitofusin 1 (MFN1), and BCL2-like 13 (BCL2L13) were measured by quantitative RT-PCR. These genes are involved in mitochondrial biogenesis, fission, fusion, and mitophagy. SIRT1, FIS1, MFN1, and BCL2L13 mRNA levels were significantly higher (p < 0.05) in the epithelial and stromal cells treated with 50 µM resveratrol than in the control cells. Additionally, mitochondrial membrane potential was significantly elevated (p < 0.05) in the epithelial and stromal cells after 50 µM resveratrol treatment. Intracellular ATP production was also significantly increased (p < 0.05) in the epithelial cells after 50 µM resveratrol treatment. Furthermore, 25 mL of resveratrol solution (100 µM) was injected into each bilateral uterine horn of the beef cattle the day after estrus, and endometrial tissues were biopsied on day 7 post-estrus (resveratrol: n = 9; control: n = 10). In the endometrium, resveratrol significantly increased (p < 0.05) the FIS1 mRNA levels and increased (p = 0.081) the SIRT1 mRNA levels compared to those in the control. After resveratrol (100 µM) administration the day after estrus, embryo transfer was performed after six days (resveratrol: n = 15; control: n = 19). Notably, conception rate was significantly increased (80.0%) after resveratrol treatment compared to that in the control group (42.1%; p < 0.05). Overall, our findings suggest that resveratrol promoted mitochondrial functions by stimulating mitochondrial biogenesis, fusion, and fission in the endometrial cells, thereby increasing the fertility of cows.