Human Umbilical Cord Mesenchymal Stem Cells Improve Premature Ovarian Failure through Cell Apoptosis of miR-100-5p/NOX4/NLRP3

Abstract

Premature ovarian failure refers to a series of symptoms of perimenopausal hot flashes, night sweats, decreased libido, vaginal dryness, insomnia, reduced menstruation, sparse hair, even amenorrhea, and even infertility before the age of 40 due to the decline of ovarian function. Premature ovarian failure is a common and difficult disease in gynecology. Its prevalence is increasing gradually, and the trend is younger. The aim of this experiment was to elucidate the role of human umbilical cord mesenchymal stem cells (HUCMSCs) in premature ovarian failure and its mechanism. HUCMSCs, KGN cells, and HEK293T cells were used in this experiment. Quantitative PCR and microarray analysis, ELISA inflammation and oxidative stress kits, RNA pull-down assay, luciferase reporter assay, proliferation assay, EDU staining, and Western blot analysis were used. In an in vitro model of premature ovarian failure, HUCMSCs attenuated inflammatory response, oxidative stress, and apoptosis. HUCMSCs ameliorated the premature ovarian failure model. The miR-100-5p expression was induced by HUCMSCs through methylation. miR-100-5p regulation influenced the role of HUCMSCs in an in vitro model of premature ovarian failure. HUCMSCs inhibited the in vitro expression of NOX4, NLRP3, and GSDMD proteins in the model. NOX4/NLRP3 signaling pathway affects the role of HUCMSCs in an in vitro model of premature ovarian failure through miR-100-5p. This experiment elucidated the role of HUCMSCs in premature ovarian failure and its mechanism, with a view to providing a clinical reference.

Bone Morphogenetic Protein 6 Induces Downregulation of Pentraxin 3 Expression in Human Granulosa Cells through the SMAD-Dependent Signaling Pathway in Women with Polycystic Ovary Syndrome

“…The human ovarian granulosa cell line (KGN cells) is a commonly used cell model in the in vitro experiments to study ovarian functions because these cells are easy to isolate, culture, and transfect and can be analyzed by immunocytochemical methods (18,19).KGN cells were cultured at 37°C in 5% CO 2 and 95% air. Dulbecco's modi ed Eagle's medium/nutrient mixture F-12 ham (DMEM/F-12; Sigma Aldrich, USA) was used to culture the cells and supplemented with penicillin (100 U/mL, Invitrogen, life technologies, USA), streptomycin sulfate (100 µ G/mL, Invitrogen, Life Technologies, USA), glutamine (1x, Invitrogen, life technologies, USA), and 10% carbon/dextran treated fetal bovine serum (10%, HyClone, USA).…”

A Review on Treatment of Premature Ovarian Insufficiency: Characteristics, Limitations, and Challenges of Stem Cell versus ExosomeTherapy

“…HUCMSCs exosomal miRNA-100-5p has acted through the NOX4/NLRP3 signaling pathway to prevent apoptotic phenomena in a POF model [67]. HUCMSCs exosomal miRNA-29a (Figure 2(b)) [54] and HUCMSCs-derived exosomes [56,68] have promoted ovarian function, improved angiogenesis, developed folliculogenesis, and restored the estrous cycle through the Wnt/β-catenin, Hippo, and PI3K/AKT signaling pathways in POI-induced rodents, respectively.…”

The dual role of mesenchymal stem cells in apoptosis regulation

“…1). Many studies have found that MSCT significantly reduce the apoptosis of diseases-related tissue cells (Table 1), which is achieved by the activation of a variety of signaling pathways [13][14][15]. More interestingly, MSCs also alleviate diseases by promoting apoptosis in some cells, such as autoimmune diseases and tumors [16][17][18].…”