Nakagawa Shinichi, Shimada Masayuki, Yanaka Kaori, Mito Mari, Arai Takashi, Takahashi Eiki, Fujita Youko, Fujimori Toshihiko, Standaert Laura, Marine Jean-Christophe, Hirose Tetsuro
RNA Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Laboratory of Reproductive Endocrinology, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.
Development. 2014 Dec;141(23):4618-27. doi: 10.1242/dev.110544. Epub 2014 Oct 30.
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.
Neat1是一种非蛋白质编码RNA，作为被称为副斑点的核体的结构成分。尽管基于细胞的研究表明Neat1是基因表达的关键调节因子，但其生理相关性仍不清楚。在这里，我们发现Neat1基因敲除（KO）小鼠尽管排卵正常，但仍随机出现无法怀孕的情况。单侧移植野生型卵巢或给予孕酮可部分挽救该表型，表明黄体功能障碍和随之而来的低孕酮水平是生育力下降的主要原因。与在大多数成年组织中观察到的微弱表达不同，Neat1在黄体中高度表达，并且在近一半的Neat1 KO小鼠中黄体组织的形成严重受损。这些观察结果表明，在尚未确定的次优条件下，Neat1对于黄体的形成以及随后的妊娠建立至关重要。
