title: The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice.
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.
authors.affiliation: RNA Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan nakagawas@riken.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Laboratory of Reproductive Endocrinology, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimada
authors.affiliation: RNA Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yanaka
authors.affiliation: RNA Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Mito
authors.affiliation: Support Unit for Animal Resources Development, Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.affiliation: Support Unit for Animal Resources Development, Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
authors.affiliation: Women's Clinic Oizumi-Gakuen, Higashi-Oizumi, Tokyo 178-0063, Japan.
authors.forename: Youko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Division of Embryology, National Institute for Basic Biology (NIBB), Okazaki 444-8787, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujimori
authors.affiliation: Laboratory for Molecular Cancer Biology, Center for the Biology of Disease, VIB, Leuven 3000, Belgium Laboratory for Molecular Cancer Biology, Center of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Standaert
authors.affiliation: Laboratory for Molecular Cancer Biology, Center for the Biology of Disease, VIB, Leuven 3000, Belgium Laboratory for Molecular Cancer Biology, Center of Human Genetics, KU Leuven, Leuven 3000, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Marine
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hirose
mesh_terms: D000818:Animals; D003338:Corpus Luteum / Q000254:growth & development* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics; D011247:Pregnancy / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; C557040:Malat1 long non-coding RNA, mouse; C577275:NEAT1 long non-coding RNA, mouse; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; C494389:paraspeckle protein 1, mouse; D011374:Progesterone
keywords: Corpus luteum; Neat1; Paraspeckles; Progesterone; Sfpq; Stochastic failure