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-Müllerian 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 GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 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 GABAB2 receptor.

Dysbiosis of Gut Microbiota Contributes to Chronic Stress in Endometriosis Patients via Activating Inflammatory Pathway

Background:Gut microbiota can interact with the central nervous system through the gut-brain axis,thus affecting the host’s chronic stress level,such as anxiety and depression.Current researches show that patients with endometriosis often have a high level of chronic stress,which will in turn aggravate endometriosis by activating theβ-adrenergic signaling pathway.Therefore,we wondered whether the gut microbiota associates with the chronic stress level in endometriosis patients,which may provide new insights on how to improve treatment.Methods:We grouped the endometriosis patients into the chronic stress group and the control group with questionnaires such as generalized anxiety disorder-7 and patient health questionnaire-9 and collected patients’fecal specimens and tissue specimens.Gut microbiota compositions were analyzed by the 16SrRNA gene sequencing-based method,and immunohistochemistry was performed to detect the activation of inflammatory pathways in endometriosis tissues.Results:We found that in patients with endometriosis,the dysbiosis of gut microbiota was associated with their stress levels.Furthermore,the levels of Paraprevotella,Odoribacter,Veillonella,and Ruminococcus were significantly reduced in chronic stressed endometriosis patients,suggestive of a disease-specific change of gut microbiota at the genus level.Compared to the healthy women,the expression levels of inflammatory cytokines,nuclear factor-κB p65,and cyclooxygenase-2 increased in the chronic stressed endometriosis patients,indicating that the dysbiosis of gut microbiota may activate the inflammatory pathway of gut-brain axis.Conclusions:We hypothesized that these new disease-specific changes of gut microbiota in chronic stressed patients with endometriosis may be a new examination target of chronic stress level.These changes may also provide new insights for psychological intervention,thus reducing the stress level and improving the prognosis of endometriosis patients.