Requirement of the 3'-UTR-dependent suppression of DAZL in oocytes for pre-implantation mouse development

PLoS Genet. 2018 Jun 8;14(6):e1007436. doi: 10.1371/journal.pgen.1007436. eCollection 2018 Jun.

Abstract

Functional oocytes are produced through complex molecular and cellular processes. In particular, the contribution of post-transcriptional gene regulation mediated by RNA-binding proteins (RBPs) is crucial for controlling proper gene expression during this process. DAZL (deleted in azoospermia-like) is one of the RBPs required for the sexual differentiation of primordial germ cells and for the progression of meiosis in ovulated oocytes. However, the involvement of DAZL in the development of follicular oocytes is still unknown. Here, we show that Dazl is translationally suppressed in a 3'-UTR-dependent manner in follicular oocytes, and this suppression is required for normal pre-implantation development. We found that suppression of DAZL occurred in postnatal oocytes concomitant with the formation of primordial follicles, whereas Dazl mRNA was continuously expressed throughout oocyte development, raising the possibility that DAZL is dispensable for the survival and growth of follicular oocytes. Indeed, follicular oocyte-specific knockout of Dazl resulted in the production of normal number of pups. On the other hand, genetically modified female mice that overexpress DAZL produced fewer numbers of pups than the control due to defective pre-implantation development. Our data suggest that post-transcriptional suppression of DAZL in oocytes is an important mechanism controlling gene expression in the development of functional oocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Embryonic Development / genetics*
  • Female
  • Gene Expression Regulation, Developmental*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oocytes / growth & development
  • Oocytes / metabolism
  • Oogenesis / genetics*
  • Ovarian Follicle / cytology
  • Ovarian Follicle / growth & development*
  • Ovarian Follicle / metabolism
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics*

Substances

  • 3' Untranslated Regions
  • DAZL protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins

Grant support

This work was supported by Grant-in-Aid for Young Scientists (B) to YK (No. 25840091), Grant-in-Aid for Scientific Research (A) to YS (No. 26251025) from Japanese society for the promotion of science (JSPS) and Scientific Research on Innovative Areas from Ministry of education, culture, sports, Science and technology (MEXT) to YS (No. 25112002), AS (No. 16H01252), and YK (No. 16H01259). KF is a Grant-in-Aid for JSPS Research Fellow (No. 16J11687). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.