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      microRNA 92b-3p regulates primordial follicle assembly by targeting TSC1 in neonatal mouse ovaries

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          ABSTRACT

          The primordial follicle pool, providing all oocytes available to a female throughout her reproductive life, is established perinatally. The formation of primordial follicle pool is regulated by precise transcriptional and post-transcriptional mechanisms. Recent studies have identified several microRNAs as post-transcriptional regulatory factors in the process of primordial follicle assembly. Here, we showed that miR-92b-3p was significantly upregulated in the stage of primordial follicle assembly in newborn mouse ovaries. Inhibiting miR-92b-3p suppressed the formation of primordial follicles, while overexpression of miR-92b-3p accelerated the processes of cyst breakdown and the following primordial follicle assembly. Accordingly, the expression of follicular development-related genes was reduced upon inhibiting of miR-92b-3p and increased under miR-92b-3p overexpression. Mechanistic studies identified TSC1 as a direct target of miR-92b-3p. miR-92b-3p could activate mTOR/Rps6 signaling through targeting and inhibiting TSC1 expression. In addition, knockdown of TSC1 showed an identical phenotype with that of miR-92b-3p overexpression in accelerating processes of cyst breakdown and primordial follicle formation. Thus, our work demonstrates that miR-92b-3p is a novel regulator of primordial follicle assembly by negatively regulating TSC1 in mTOR/Rps6 signaling.

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          Author and article information

          Journal
          Cell Cycle
          Cell Cycle
          KCCY
          kccy20
          Cell Cycle
          Taylor & Francis
          1538-4101
          1551-4005
          2019
          6 April 2019
          : 18
          : 8
          : 824-833
          Affiliations
          [a ] State Key Laboratory of Reproductive Medicine, Nanjing Medical University , Nanjing, China
          [b ] Department of Reproductive Medicine, Maternal and Child Health Care Hospital of Nantong City , Nantong, China
          [c ] Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University , Nanjing, China
          [d ] Department of Microbiology, Nanjing Medical University , Nanjing, China
          Author notes
          CONTACT Xuesen Zhang xuesenzhang@ 123456njmu.edu.cn
          [*]

          These authors contributed equally to this work.

          Article
          PMC6527271 PMC6527271 6527271 1593648
          10.1080/15384101.2019.1593648
          6527271
          30880550
          © 2019 Informa UK Limited, trading as Taylor & Francis Group
          Page count
          Figures: 6, References: 43, Pages: 10
          Funding
          Funded by: National Natural Science Foundation of China 10.13039/501100001809
          Award ID: 81501797 to XQL
          This work was supported by National Key Research and Development Program of China [2018YFC1003703, 2018YFC1004203], National Natural Science Foundation of China [81501797 to XQL], the Key Project of Science and Technology Innovation of Nanjing Medical University [2017NJMUCX007], and Jiangsu Six Talent Peaks Project.
          Categories
          Research Paper

          TSC1, mTOR, primordial follicle formation, Mir-92b-3p

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