RESUMEN
Successful mouse embryo implantation requires a receptive uterus and an activated blastocyst. A large number of genes, cytokines, and other factors are involved in the process. MicroRNAs (miRNAs) regulate the expression of many genes, and previous studies have investigated the relationship between miRNA expression and embryo implantation. In this study, we show that mmu-microRNA-200a (mmu-miR-200a) is expressed in a spatiatemporal manner during implantation in mouse uterus and found that phosphatase and tensin homolog (PTEN), SON, and programmed cell death 4 (Pdcd4) are the target genes of mmu-miR-200a by bioinformatics analysis. In vitro gain and loss of function experiments confirm that PTEN, a critical gene for cell proliferation and apoptosis, is the target gene of mmu-miR-200a. Our experiments also show that injection of the uterine horn with mmu-miR-200a lentivirus leads to a decreased implantation rate. Collectively, our results suggest that mmu-miR-200a affects embryo implantation by regulating PTEN protein expression. Thus, clarifying the physiological functions of uterine miRNAs will help to elucidate the embryo implantation process and may even contribute to curing infertility and inventing new contraceptives.
Asunto(s)
Implantación del Embrión , MicroARNs/metabolismo , Fosfohidrolasa PTEN/metabolismo , Útero/enzimología , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proliferación Celular , Células Cultivadas , Biología Computacional , Femenino , Regulación del Desarrollo de la Expresión Génica , Vectores Genéticos , Lentivirus/genética , Ratones , MicroARNs/genética , Fosfohidrolasa PTEN/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Transfección , Regulación hacia Arriba , Útero/fisiopatologíaRESUMEN
The 'fetal origin hypothesis' suggests that metabolic diseases are directly related to poor nutritional status in early life. Thus, a high birth weight (HBW) may pose a lower risk than normal birth weight. Overweight and overnutrition are among the most widely recognized risk factors of metabolic diseases. To explore the possible effects of HBW on blood pressure and hypertension, a systematic review was performed. The PubMed and Embase databases were searched for relevant studies. The outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension. We included all of the studies that assessed the differences in outcomes for children aged >1 year between those born with normal birth weight (birth weight between 2500 and 4000 g or between the 10th and 90th percentiles for their gestational age) and those born with HBW (birth weightî¶4000 g or î¶90th percentile for their gestational age). The outcomes were analyzed descriptively and by conducting a meta-analysis. Thirty-one studies satisfied the inclusion criteria. The mean difference in blood pressure and the relative risk of hypertension between individuals with HBW and individuals with normal birth weight was inversely associated with age. SBP and DBP, as well as the prevalence of hypertension, were higher in younger children with HBW but lower in older adults with HBW compared with individuals with normal birth weight. The findings suggested that an individual with HBW is prone to hypertension and higher blood pressure during childhood. However, a 'catch-down' effect in the elevation of blood pressure is observed in subjects with HBW as they grow older. Thus, older individuals with HBW are less susceptible to hypertension than those with normal birth weight.
