Baicalein Ameliorates Chronic Stress-Mediated Ovarian Dysfunction by Upregulating the Expression of Gamma-Aminobutyric Acid B2 Receptor

Background: The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model. Methods: Forty female C57BL/6 mice were randomly divided into four groups as follows: the normal saline group (control, n = 10), the daily stress group (daily stress, n = 10), the baicalein group (baicalein, n = 10), and the daily stress + baicalein group (daily stress + baicalein, n = 10). For the daily stress model, we used a restricted stress model. Baicalein (10 mg/kg) was administered by gavage every day, and control mice received normal saline equivalently. Biopsy specimens were harvested after 4 weeks. Measurement of norepinephrine (NE) in serum was performed to assess the psychological stress level of the mice. In addition, histological changes of the uterus and ovaries and the levels of anti-Mullerian hormone (AMH) in serum were assessed to evaluate changes in ovarian function. To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction, immunohistochemical methods, and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid (GABA) receptors. Results: Compared with values in the control group, serum NE concentrations were significantly increased (P < 0.001), AMH concentrations were markedly decreased (P < 0.01), the thickness of the endometrium was clearly reduced, and the percentage of atretic follicles was significantly increased in the daily stress group (P < 0.001), indicating that the chronic stress model was successfully established. In contrast, compared with values in the daily stress group, serum NE concentrations were significantly reduced (P < 0.001), AMH concentrations were significantly enhanced (P < 0.05), the thickness of the endometrium was clearly increased, and the percentage of atretic follicles was significantly reduced (P < 0.001) in the daily stress + baicalein group, indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress. Moreover, the expression of the GABA(B2) receptor in the daily stress group was significantly reduced (P < 0.01). In contrast, treatment with baicalein resulted in increased expression of the GABA(B2) receptor (P < 0.01). Conclusions: Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction, and the mechanism can be attributed, in part, to the increased expression of the GABA(B2) receptor.