Context. Polycystic ovary syndrome (PCOS) is a gynecological endocrine disease, and approximately 60 of patients with PCOS have different degrees of insulin resistance (IR). The regulatory role of metabolic networks in human follicular fluid (FF) related to IR in PCOS remains unclear. Aims. To explore the effect of IR on the metabolism of PCOS by analyzing the changes in FF metabolites in PCOS patients who are undergoing assisted reproductive technology based on the metabonomic platform of ultraperformance gas chromatography coupled to mass spectrometry (GC/MS). Method. Eight PCOS patients with IR (PCOS-IR) and 8 PCOS patients without IR (PCOS-NIR) were enrolled. All patients received controlled ovarian stimulation by using the gonadotropin-releasing hormone (GnRH) antagonist protocol, and the FF of a single dominant follicle was collected on the day of oocyte retrieval. The metabolite profiles of the FF were determined by GC/MS. Key Results. A total of 20 differentially expressed metabolites in FF were identified. Compared with levels in the PCOS-NIR group, stearic acid, palmitic acid, pentadecanoic acid, stigmasterol, citric acid, isocitric acid, thymine, and pyruvic acid in FF were significantly increased in the PCOS-IR group. Lithocholic acid and sinapinic acid in FF decreased significantly. The affected metabolic pathways with potential regulatory roles were identified by KEGG annotation. Conclusion. Compared with the PCOS-NIR group, the PCOS-IR group showed more significant metabolic abnormalities. Implications. These results will help us to understand the pathogenesis of PCOS combined with IR and will provide new clues for studying metabolic disorders associated with PCOS, e.g., IR.

Thin endometrium (TE), which mainly occurs as a result of severe damage to the endometrial basalis, is one of the prominent etiologies of menstrual abnormalities, infertility, and recurrent miscarriage in women. Previous studies have demonstrated that mesenchymal stem cells (MSCs) are considered ideal cells with multipotency for regenerative medicine and exhibit therapeutic effects on TE through their cellular secretions. However, there is limited research on strategies to enhance MSC secretion to improve their therapeutic efficacy. Herein, we isolated menstrual blood–derived mesenchymal stem cells (MenSCs) from menstruation and transformed them into decidualized stromal cells (DSCs), which are specialized cells with enhanced secretory functions. To assess the therapeutic potential of DSCs compared to MenSCs, we conducted a series of experiments in cells and animals. The results demonstrated that DSCs exhibited changes in morphology compared to MenSCs, with a decrease in cell proliferation but a significant improvement in secretion function. Furthermore, DSCs facilitated the restoration of endometrial thickness and increased the number of glands and blood vessel formation. Most importantly, the pregnancy rates in rats were effectively restored, bringing them closer to normal levels. These findings greatly contribute to our understanding of stem cell therapy for TE and strongly suggest that DSCs could hold significant promise as a potential treatment option for TE.

Intrauterine adhesion (IUA), resulting from uterine trauma, is one of the major causes of female infertility. Previous studies have demonstrated that endometrial mesenchymal stem cells (eMSC) have therapeutic effects on IUA through cellular secretions. It is particularly true for most of the pre-clinical experiments performed on multiple animal models, as human-derived eMSC cannot maintain long-term engraftment in animals. Whether tissue-specific MSCs from allogeneic origin can engraft and exert long-term therapeutic efficacy has yet to be thoroughly explored. We established a rat IUA model to study the long-term engraftment and therapeutic effects of eMSC derived from humans and rats. Human and rat eMSC were isolated and verified by the expression of cell surface markers and the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. The cells were then labeled by green fluorescence proteins (GFP) and transplanted to the rat uterus ex vivo and in vivo. The engraftment was investigated by the expression of GFP at different days after transplantation. Assessed the therapeutic effects by examining the endometrial thickness, the number of glands, and the pregnancy outcome. Significantly, we conducted a thorough assessment of the local cellular immune response following both xenograft and allograft transplantation. H-eMSC were eliminated by rats’ immune systems within three days after transplantation. In constrast, R-eMSC successfully engrafted and persisted in rat tissue for over ten days. Notably, R-eMSC significantly improved the pregnancy rate by enhancing endometrial thickness and increasing the number of glands, while also reducing fibrosis in rat IUA models. Additionally, the immune response to R-eMSC was generally less aggressive compared to that of xenogeneic MSCs. Tissue-specific MSCs from the allogeneic origin can integrate into the repaired tissue and exert long-term therapeutic efficacy in the model of IUA. This study indicates that in addition to secreting therapeutic factors short-time, tissue-specific MSCs may engraft and participate in long-time tissue repair and regeneration.

Thin endometrium (TE) is a significant factor contributing to fertility challenges, and addressing this condition remains a central challenge in reproductive medicine. Menstrual blood–derived mesenchymal stem cells (MenSCs) play a crucial role in tissue repair and regeneration, including that of TE. The Wnt signaling pathway, which is highly conserved and prevalent in eukaryotes, is essential for cell proliferation, tissue development, and reproductive functions. MALAT1 is implicated in various transcriptional and molecular functions, including cell proliferation and metastasis. However, the combined effects of the Wnt signaling pathway and the long non-coding RNA (lncRNA) MALAT1 on the regulation of MenSCs’ regenerative capabilities in tissue engineering have not yet been explored. To elucidate the regulatory mechanism of MALAT1 in TE, we analyzed its expression levels in normal endometrium and TE tissues, finding that low expression of MALAT1 was associated with poor clinical prognosis. In addition, we conducted both in vitro and in vivo functional assays to examine the role of the MALAT1/miR-7-5p/TCF4 axis in cell proliferation and migration. Techniques such as dual-luciferase reporter assay, fluorescent in situ hybridization, and immunoblot experiments were utilized to clarify the molecular mechanism. To corroborate these findings, we established a TE model and conducted pregnancy experiments, demonstrating a strong association between MALAT1 expression and endometrial fertility. In conclusion, our comprehensive study provides strong evidence supporting that lncRNA MALAT1 modulates TCF4 expression in the Wnt signaling pathway through interaction with miR-7-5p, thus enhancing MenSCs-mediated improvement of TE and improving fertility.

Decidualization of endometrial mesenchymal stem cells (ESCs) is crucial for the implantation of the embryo. Thin endometrium (TE) can impair endometrial re