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

Cell Cycle. 2019 Apr;18(8):824-833. doi: 10.1080/15384101.2019.1593648. Epub 2019 Apr 6.

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.

Keywords: Mir-92b-3p; TSC1; mTOR; primordial follicle formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Female
  • Gene Expression Regulation / genetics
  • Gene Knockdown Techniques
  • Male
  • Mice
  • Mice, Inbred ICR
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oocytes / metabolism*
  • Ovarian Follicle / metabolism*
  • Ovary / metabolism
  • Ribosomal Protein S6 / metabolism
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Transfection
  • Tuberous Sclerosis Complex 1 Protein / genetics
  • Tuberous Sclerosis Complex 1 Protein / metabolism*
  • Up-Regulation

Substances

  • MicroRNAs
  • Mirn92 microRNA, mouse
  • Ribosomal Protein S6
  • Tsc1 protein, mouse
  • Tuberous Sclerosis Complex 1 Protein
  • ribosomal protein S6, mouse
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases

Grants and funding

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.