A novel, noncoding-RNA-mediated, post-transcriptional mechanism of anti-Mullerian hormone regulation by the H19/let-7 axis
| Autor: | Bahar Uslu, Na Zhang, Ying Jiang, Amanda N. Kallen, Yong Chen, Joshua Johnson, Chunrong Qin, Yanhong Fan, Xi Xia |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Anti-Mullerian Hormone endocrine system Biology Andrology 03 medical and health sciences Follicle Follicle-stimulating hormone Mice 0302 clinical medicine Follicular phase medicine Animals Humans Ovarian reserve Cells Cultured Mice Knockout Gene knockdown 030219 obstetrics & reproductive medicine urogenital system Anti-Müllerian hormone Cell Biology General Medicine Antral follicle Oocyte female genital diseases and pregnancy complications Mice Inbred C57BL MicroRNAs 030104 developmental biology medicine.anatomical_structure Reproductive Medicine embryonic structures biology.protein Female RNA Interference RNA Long Noncoding Corrigendum hormones hormone substitutes and hormone antagonists Research Article Signal Transduction |
| Zdroj: | Biology of reproduction. 100(1) |
| ISSN: | 1529-7268 |
| Popis: | In reproductive age women, the pool of primordial follicles is continuously depleted through the process of cyclic recruitment. Anti-Mullerian hormone (AMH) both inhibits the initial recruitment of primordial follicles into the growing pool and modulates the sensitivity of growing follicles to follicle stimulating hormone. Thus, AMH may be an important modulator of female infertility and ovarian reserve; however, the mechanisms regulating AMH remain unclear. To evaluate AMH levels in the absence of H19 lncRNA, H19 knockout (H19KO) mice were evaluated for analysis of ovarian AMH gene expression, protein production, and reproductive function, including assessment of follicle numbers and litter size analysis. To further investigate regulation of AMH by the H19/let-7 axis, let-7 binding sites on AMH were predicted, and in vitro studies of the effect of H19 knockdown/overexpression with let-7 rescue were performed. Lastly, response to superovulation was assessed via oocyte counts and estradiol measurements. The H19KO mouse demonstrates subfertility and accelerated follicular recruitment with increased spontaneous development of secondary, preantral, and antral follicles. Ovaries of H19KO mice have decreased AMH mRNA and protein, and AMH mRNA has a functional let-7 binding site, suggesting a plausible ncRNA-mediated mechanism for AMH regulation by H19/let-7. Lastly, in the absence of H19, superovulation results in higher estradiol and more oocytes, suggesting that H19 functions to limit the number of follicles that mature, produce estradiol, and ovulate. Thus, AMH’s inhibitory actions are regulated at least in part by H19, likely via let-7, marking this ncRNA pair as important regulators of the establishment and maintenance of the follicular pool. |
| Databáze: | OpenAIRE |
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