The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice

Development. 2014 Dec;141(23):4618-27. doi: 10.1242/dev.110544. Epub 2014 Oct 30.

Abstract

Neat1 is a non-protein-coding RNA that serves as an architectural component of the nuclear bodies known as paraspeckles. Although cell-based studies indicate that Neat1 is a crucial regulator of gene expression, its physiological relevance remains unclear. Here, we find that Neat1 knockout (KO) mice stochastically fail to become pregnant despite normal ovulation. Unilateral transplantation of wild-type ovaries or the administration of progesterone partially rescued the phenotype, suggesting that corpus luteum dysfunction and concomitant low progesterone were the primary causes of the decreased fertility. In contrast to the faint expression observed in most of the adult tissues, Neat1 was highly expressed in the corpus luteum, and the formation of luteal tissue was severely impaired in nearly half of the Neat1 KO mice. These observations suggest that Neat1 is essential for the formation of the corpus luteum and for the subsequent establishment of pregnancy under a suboptimal condition that has not yet been identified.

Keywords: Corpus luteum; Neat1; Paraspeckles; Progesterone; Sfpq; Stochastic failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Luteum / growth & development*
  • Corpus Luteum / metabolism
  • DNA Primers / genetics
  • Female
  • Fertility / genetics
  • Fertility / physiology
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Pregnancy / physiology*
  • Progesterone / blood
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / physiology*

Substances

  • DNA Primers
  • Malat1 long non-coding RNA, mouse
  • NEAT1 long non-coding RNA, mouse
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • paraspeckle protein 1, mouse
  • Progesterone