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Comment |
MiR-423-5p may regulate ovarian response to ovulation induction via CSF1. Xie S et al. (2020) We have previously shown that hsa-miR-423-5p expression in ovarian granulosa cells is decreased in high ovarian response populations. The objective of the present study was to find the target gene and mechanism for miR-423-5p involved in ovarian response regulation. (a) TargetScan was used to predict the target gene of hsa-miR-423-5p. (b) A model for hsa-miR-423-5p overexpression or inhibition was constructed by transfecting KGN cells with lentivirus. CSF1 mRNA and protein expression and luciferase activity were measured. (c) The cell cycles of control and lentivirus treated KGN cells were analyzed. Western blot was used to measure the expression of CDKN1A in KGN cells. (d) The concentration of E2 in KGN cell culture medium were measured. (a) TargetScan revealed that the 3' un-translated region of CSF1 matched 11 bases at the 5' end of miR-423-5p, making it a likely target gene. (b) Overexpression or inhibition of miR-423-5p were associated with respective decreases or increases in CSF1 expression (both mRNA and protein) (p < 0.05) and luciferase activity (p < 0.05). (c) When miR-423-5p expression increased, the number of G0/G1 phase cells and the expression of CDKN1A protein increased while estradiol concentrations in the cell culture solution decreased (p < 0.05). However, when miR-423-5p expression decreased, the number of S phase cells increased and E2 concentrations increased while the expression of CDKN1A protein decreased (p < 0.05). Colony stimulating factor 1 is a target gene of miR-423-5p and that it may regulate ovarian response to ovulation induction by affecting granulosa cells proliferation and estrogen secretion.//////////////////MicroRNA Expression is Altered in Granulosa Cells of Ovarian Hyperresponders. Xie S et al. (2016) Controlled ovarian stimulation plays an integral role in assisted reproduction technology, but individual patients have different responses to exogenous gonadotropins. In order to determine whether microRNAs (miRNAs) have a regulatory role in ovarian response, we profiled the expression of microRNAs in isolated ovarian granulosa cells collected from ovarian hyperresponders and normal responders using microarrays and validated the expression of selected miRNAs using quantitative polymerase chain reaction (PCR). There were 81 miRNAs differentially expressed between the 2 groups, with 45 increased and 36 decreased in the high response group. Bioinformatics analysis of these altered miRNAs and their target genes revealed some significantly enriched pathways, including regulation of the cell cycle, transcription, cell proliferation, and gonadotrophin releasing hormone signaling pathway. The expression of hsa-miR-513a-5p, hsa-miR-27b-3p, hsa-miR-19b-3p, hsa-miR-3201, hsa-miR-423-5p, hsa-miR-193b-5p, and hsa-miR-202-3p was validated by real-time PCR. Hsa-miR-423-5p, predicted to target anti-Mullerian hormone, cytochrome P450, family 19, subfamily A, polypeptide 1, methylenetetrahydrofolate reductase, progesterone receptor, and follicle stimulating hormone, β-polypeptide was found to have significantly decreased expression in the hyperresponders (P = .023). Hsa-miR-193b-5p also showed a tendency to be significantly decreased in the hyperresponders (P = .093). In conclusion, our findings provide evidence for altered miRNA expression in granulosa cells of women with ovarian hyperresponse, suggesting a role of miRNAs in regulating ovarian response to gonadotropins.//////////////////
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Mutations |
1 mutations
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.//////////////////
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