ABSTRACT
BACKGROUND: Myotonic dystrophy type 1 (DM1), one of the most common forms of adult-onset muscular dystrophy, is caused by abnormally expanded CTG repeats in the 3' untranslated region of the DMPK gene. The CUG repeats transcribed from the expanded CTG repeats sequestrate a splicing factor, MBNL1, causing the clinical symptoms in DM1. Nowadays, only symptomatic treatments are available for DM1, and no rational therapy is available. Recently, upregulation of MBNL1 expression has been found to be one of the promising therapies for DM1. METHODS: All experiments were conducted in the C2C12 myoblasts and HSALR mice, a DM1 mouse model. Real-time PCR and western blot were used to detect the mRNA and protein level, respectively. The rotarod exercise, grip strength and hanging time were used to evaluate the muscle strength of mice. RESULTS: In this study, we demonstrated that calcitriol, an active form of vitamin D3, increased MBNL1 in C2C12 mouse myoblasts as well as in HSALR mice model for DM1. In HSALR mice model, calcitriol improved muscle strength, and corrected aberrant splicing in skeletal muscle. Besides, calcitriol reduced the number of central nuclei, and improved muscle histopathology in HSALR mice. In addition, we identified that calcitriol upregulated MBNL1 expression via activating the promoter of Mbnl1 in C2C12 myogenic cells. CONCLUSION: Our study suggests that calcitriol is a potential pharmacological strategy for DM1 that enhances MBNL1 expression.
Subject(s)
Myotonic Dystrophy , Mice , Animals , Myotonic Dystrophy/drug therapy , Myotonic Dystrophy/genetics , Myotonic Dystrophy/metabolism , Calcitriol/pharmacology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Myoblasts/metabolism , Disease Models, Animal , Muscle, Skeletal/pathology , Alternative Splicing , DNA-Binding Proteins/metabolismABSTRACT
OBJECTIVE: To assess the relationships among human follicular fluid-induced acrosome reaction, sperm morphology and in vitro fertilization rates. METHODS: The relationships among human follicular fluid-induced acrosome reaction, sperm morphology and in vitro fertilization rates were investigated by Spearman rank correlation in 79 infertile couples. And the sperm morphology analysis was performed by crystal violet staining and based on strict criteria. RESULTS: A significant positive correlation was found between the percentage of human follicular fluid-induced acrosome reaction and that of normal sperm morphology (n = 49, r = 0.3763, P < 0.01), but no significant correlation was observed either between the percentage of human follicular fluid-induced acrosome reaction and in vitro fertilization rates or between that of normal sperm morphology and in vitro fertilization rates (n = 21, r = 0.2666, P > 0.05 and n = 50, r = 0.0018, P > 0.05, respectively). CONCLUSION: There is a significant positive correlation between the percentage of human follicular fluid-induced acrosome reaction and that of normal sperm morphology, but no such correlation either between the percentage of human follicular fluid-induced acrosome reaction and in vitro fertilization rates or between that of normal sperm morphology and in vitro fertilization rates.
