BackgroundChemotherapy-induced premature ovarian failure (POF) is a severe complication affecting tumor patients at a childbearing age. Mesenchymal stem cells (MSCs) can partially restore the ovarian structure and function damaged by chemotherapy. miR-21 is a microRNA that can regulate cell apoptosis. This study discusses the repair effect and mechanism of MSCs overexpressing miR-21 on chemotherapy-induced POF.MethodsRat MSCs and granulosa cells (GCs) were isolated in vitro. MSCs were transfected with miR-21 lentiviral vector (LV-miR-21) to obtain MSCs stably expressing miR-21 (miR-21-MSCs). The microenvironment of an ovary receiving chemotherapy was mimicked by adding phosphamide mustard (PM) into the cellular culture medium. The apoptosis rate and the mRNA and protein expression of target genes PTEN and PDCD4 were detected in MSCs. Apoptosis was induced by adding PM into the culture medium for GCs, which were cocultured with miR-21-MSCs. The apoptosis rate and the mRNA and protein expression of PTEN and PDCD4 were detected. The chemotherapy-induced POF model was built into rats by intraperitoneal cyclophosphamide injection. miR-21-MSCs were transplanted into the bilateral ovary. The rats were sacrificed at 15, 30, 45, and 60 days after the last injection. The ovarian weights, follicle count, estrous cycle, and sex hormone levels (estradiol (E2) and follicle-stimulating hormone (FSH)) were detected. Apoptosis of GCs was determined by TUNEL assay. The miR-21 and mRNA and protein expression of PTEN and PDCD4 were determined.ResultsThe apoptosis decreased in MSCs transfected with miR-21. The mRNA and protein expression of target genes PTEN and PDCD4 was downregulated. GCs cocultured with miR-21-MSCs showed a decreased apoptosis, an upregulation of miR-21, and a downregulation of PTEN and PDCD4. Following the injection of miR-21-MSCs, the ovarian weight and follicle counts increased; E2 levels increased while FSH levels decreased, with less severe apoptosis of GCs. The miR-21 expression in the ovaries was upregulated, while the mRNA expression and protein expression of PTEN and PDCD4 were downregulated.ConclusionsOverexpression of miR-21 in MSCs promoted efficacy against chemotherapy-induced POF and its improvement of the repair effect was related to the inhibition of GC apoptosis by targeting PTEN and PDCD4.

The diagnosis of endometriosis is typically delayed by years for the unexclusive symptom and the traumatic diagnostic method. Several studies have demonstrated that gut microbiota and cervical mucus potentially can be used as auxiliary diagnostic biomarkers. However, none of the previous studies has compared the robustness of endometriosis classifiers based on microbiota of different body sites or demonstrated the correlation among microbiota of gut, cervical mucus, and peritoneal fluid of endometriosis, searching for alternative diagnostic approaches. Herein, we enrolled 41 women (control, n = 20; endometriosis, n = 21) and collected 122 well-matched samples, derived from feces, cervical mucus, and peritoneal fluid, to explore the nature of microbiome of endometriosis patients. Our results indicated that microbial composition is remarkably distinguished between three body sites, with 19 overlapped taxa. Moreover, endometriosis patients harbor distinct microbial communities versus control group especially in feces and peritoneal fluid, with increased abundance of pathogens in peritoneal fluid and depletion of protective microbes in feces. Particularly, genera of Ruminococcus and Pseudomonas were identified as potential biomarkers in gut and peritoneal fluid, respectively. Furthermore, novel endometriosis classifiers were constructed based on taxa selected by a robust machine learning method. These results demonstrated that gut microbiota exceeds cervical microbiota in diagnosing endometriosis. Collectively, this study reveals important insights into the microbial profiling in different body sites of endometriosis, which warrant future exploration into the role of microbiota in endometriosis and highlighted values on gut microbiota in early diagnosis of endometriosis.

Ovarian injury because of chemotherapy can decrease the levels of sexual hormones and potentia generandi of patients, thereby greatly reducing quality of life. The goal of this study was to investigate which transplantation method for human umbilical cord mesenchymal stem cells (HUMSCs) can recover ovarian function that has been damaged by chemotherapy. A rat model of ovarian injury was established using an intraperitoneal injection of cyclophosphamide. Membrane-labelled HUMSCs were subsequently injected directly into ovary tissue or tail vein. The distribution of fluorescently labelled HUMSCs, estrous cycle, sexual hormone levels, and potentia generandi of treated and control rats were then examined. HUMSCs injected into the ovary only distributed to the ovary and uterus, while HUMSCs injected via tail vein were detected in the ovary, uterus, kidney, liver and lung. The estrous cycle, levels of sex hormones and potentia generandi of the treated rats were also recovered to a certain degree. Moreover, in some transplanted rats, fertility was restored and their offspring developed normally. While ovary injection could recover ovarian function faster, both methods produced similar results in the later stages of observation. Therefore, our results suggest that transplantation of HUMSCs by tail vein injection represents a minimally invasive and effective treatment method for ovarian injury.