β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota

Abstract

Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota.Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανβ3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing.Results: With the treatment of β-sitosterol and β-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανβ3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed.Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.

Parishin From Gastrodia Elata Ameliorates Aging Phenotype in Mice in a Gut Microbiota-Related Manner

“…In addition, the parishin treatment-improved metabolite β-sitosterol is a plant-derived natural bioactive compound with various pharmacological activities, such as hypolipidemic, anti-inflammatory, antitumor, tissue repair and antiaging activities ( Haiyuan et al, 2019 ; Cheng et al, 2020 ), and is used to treat fatty liver, type II diabetes, and arthritis ( Gumede et al, 2020 ; Ramalingam et al, 2020 ). The positive correlation between β-sitosterol and bacterial taxa from Prevotellaceae has been reported in different animal models ( Xia et al, 2020 ; Yu et al, 2021 ), which is consistent with our findings. However, the mechanism by which the gut microbiota regulates β-sitosterol metabolism is still unclear and needs to be further studied.…”

Modified Banxia Xiexin Decoction Ameliorates Polycystic Ovarian Syndrome With Insulin Resistance by Regulating Intestinal Microbiota

“…It also could be observed that Allobaculum had a decreasing trend and norank_f_Muribaculaceae bacteria had an increasing trend in the model group while showing opposite changes after treatment. Although the specific functions of these two bacteria are still unclear, studies have reported that Muribaculaceae was linked to obesity and had an increasing abundance in obese mice ( Chevalier et al., 2020 ; Liu et al., 2021 ; Yu et al., 2021 ), and Allobaculum was inversely proportional to fat quality ( Cox et al., 2014 ), suggesting that they may be related to lipid metabolism.…”

Hyperandrogenism and Polycystic ovary syndrome: Effects in pregnancy and offspring development

“…Several studies developed in PCOS animal models have reported a reduced expression of LIF in the endometrium (C. Li et al, 2019; S.‐Y. Li, Song, et al, 2016; Y. Yu, Cao, et al, 2021). Moreover, gene expressions of Lif were also significantly lower in patients with PCOS (Kara et al, 2019).…”