Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Characterization of Serum MicroRNAs Profile of PCOS and Identification of Novel Non-Invasive Biomarkers. Long W 2014 et al. Background: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. Method and Results: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c) were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS. 2014 S. Karger AG, Basel. /////////////////////////

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Role of microRNAs in premature ovarian insufficiency. Guo Y et al. (2017) Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea lasting for a minimum of 4 months. The typical characteristics comprised of declined estrogen and raised serum concentrations of follicle-stimulating hormone (FSH) in women <40-year-old, primarily originating from iatrogenic factors, karyotypic abnormalities, and genetic factors. However, the etiology of POI remains unknown in approximately 90% of cases. POI could lead to infertility, osteoporosis, cardiovascular disorder, and cognitive dysfunction. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs (ncRNAs) that can mediate post-translational silencing of the genes involved in the regulation of proliferation, differentiation, apoptosis, development, tumorigenesis, and hematopoiesis. Recently, the regulatory functions of miRNAs in the development of POI have been the topic of intensive research. The present review addresses the association of miRNAs' machinery genes (Dicer, Drosha, and XPO5) with POI and the miRNA expression profiles in the plasma of patients with POI. In addition, several specific miRNAs (miR-23a, miR-27a, miR-22-3p, miR-146a, miR-196a, miR-290-295, miR-423, and miR-608) related to POI are also examined in order to highlight the issues that deserve further investigation. A thorough understanding of the exact regulatory roles of miRNAs is imperative to gain novel insights into the etiology of idiopathic POI and offer new research directions in the field.//////////////////

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Increased risk of polycystic ovary syndrome (PCOS) associated with CC genotype of miR-146a gene variation. Ebrahimi SO et al. (2018) Polycystic ovary syndrome (PCOS) is an endocrinopathy in reproductive-age women believed to be affected by several genetics and environmental factors or both. Different miRNAs are one of such genetic factors that their associations with PCOS have been implicated. For instance, miR-146a that is well known for strongly regulating the immune response and inflammation was upregulated in serum plasma, follicular fluid and granulosa cells of PCOS patients. Different studies have shown that genetic changes in pre-miRNA can cause change in the expression or biological function of mature miRNA. Therefore, the main aim of this study was to investigate the association of miR-146a gene variation (rs2910164) with the susceptibility to PCOS. This study consists of 180 patients with PCOS and 192 healthy women matched by age and geographical region. Genotyping were determined by using PCR-RFLP in all subjects. The genotype frequency and allele distributions of all subjects were evaluated using Fisher's exact test directed by SPSS v.20. The genotype and allele frequencies of the miR-146a polymorphism (rs2910164) significantly differ between PCOS and healthy controls. The frequencies of CC genotype (p = .054) and 'C' allele (p = .0001) of the miR-146a variant indicated a significant incidence in cases compared to controls. Such association was obtained in co-dominant (OR = 3.16) and dominant (OR = 2.29) models. Result of this study can be proposed that women with miR-146a variation are at a higher risk for developing PCOS, which can be due to up-regulation of miR-146a.//////////////////