ABSTRACT
Idiopathic diseases of the reproductive system are important factors leading to male infertility. Many studies have shown that microRNAs (miRNAs) regulate the expression of multiple genes that play a significant role in spermatogenesis and development. We previously showed that microRNA-210 (miR-210) is one of the markedly upregulated microRNAs in the testes of sterile males with maturation arrest (MA). However, the role of miR-210 in spermatogenesis remains unknown. In this study, we found that miR-210 is highly expressed not only in patients with MA but also in patients with cryptorchidism. In addition, miR-210 inhibits the expression of Nuclear Receptor Subfamily 1, Group D, Member 2 (NR1D2) both in vitro and in vivo, particularly in cryptorchidic tissues. To facilitate further research, we established a mouse model of cryptorchidism and were surprised to discover that the miR-210 expression pattern was in accordance with that of patients with cryptorchidism. Thus, we propose that miR-210 may serve as a biomarker of cryptorchidism in clinical tests.
Subject(s)
Cryptorchidism/genetics , Gene Expression Regulation , MicroRNAs/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Repressor Proteins/genetics , Animals , Azoospermia/genetics , Azoospermia/metabolism , Cell Line, Tumor , Cryptorchidism/metabolism , HEK293 Cells , Humans , Male , Mice , Receptors, Cytoplasmic and Nuclear/metabolism , Repressor Proteins/metabolism , Spermatogenesis/genetics , Spermatogonia/metabolism , Testis/metabolism , Up-RegulationABSTRACT
This study aimed to evaluate the efficacy and safety of topical treatment with natural herbal medicines on recurrent aphthous stomatitis (RAS). Nine electronic databases were searched to identify the randomized controlled trials and clinical controlled trials that reported the potential effect of natural herbal medicines on RAS published in Chinese or English. Ulcer size and duration, and remission of pain were assessed as main outcome measures. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systemic Review of Interventions and Rev Man software. Thirteen trials with a total of 1,515 patients were included in the present analysis, which showed that topical treatment with natural herbal medicines seemed to benefit RAS patients by reducing ulcer size, shortening ulcer duration, and relieving pain without severe side effects. In conclusion, there is some evidence of the efficacy of topically applied natural herbal medicines with regards to improved RAS outcome measures and fewer side effects. However, given the limitations of this study, the evidence remains insufficient. Well-designed and high-quality randomized controlled trials are required for further exploration.
Subject(s)
Plant Preparations , Plants, Medicinal , Stomatitis, Aphthous , Humans , Administration, Topical , Pain/drug therapy , Pain/etiology , Phytotherapy/adverse effects , Phytotherapy/methods , Plant Preparations/administration & dosage , Plant Preparations/adverse effects , Plant Preparations/pharmacology , Plants, Medicinal/chemistry , Randomized Controlled Trials as Topic , Recurrence , Stomatitis, Aphthous/drug therapy , Stomatitis, Aphthous/pathologyABSTRACT
Male germ cells with aberrant DNA damage are the weighted factor contributing to male infertility. Mounting evidence shows that DNA damage in male germ cells impairs spermatogenesis and lowers fecundity. MicroRNAs (miRNAs) regulating expression of multiple genes play a significant role in spermatogenesis. Our previous results have shown that microRNA-383 (miR-383) is one of the notable down-regulated microRNAs in the testes of sterile males with maturation arrest (MA) and is located predominantly in spermatogonia and primary spermatocytes. However, the role that miR-383 plays in DNA damage during spermatogenesis remains unknown. In this study, we found that miR-383 inhibited the focal formation and abundance of γH2AX, which is the major marker of sites of DNA damage, with or without ultraviolet irradiation and cisplatin in testicular embryonal carcinoma (NT-2) cells. In addition, NT-2 cells were remarkably sensitized to DNA damage reagent (cisplatin) by forcing expression of miR-383 and silencing expression of protein phosphatase 1, regulatory subunit 10 (PNUTS). By constructing Renilla luciferase reporters and co-transfecting miR-383 and reporters in NT-2 cells, we identified that PNUTS was a valid target of miR-383. Further results demonstrated that the repression of the phosphorylated form of H2AX by miR-383 was due to independent depletion of PNUTS and cell cycle arrest. In conclusion, we found a novel function of miR-383 in the DNA damage pathway. miR-383 impairs the phosphorylation of H2AX by targeting PNUTS and inducing cell cycle arrest independently, as well as sensitizing NT-2 cells to cisplatin.
