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Calcineurin/NFAT Pathway: A Novel Regulator of Parturition
Authors:Chisa Tabata  Kazuhide Ogita  Keisuke Sato  Hitomi Nakamura  Zhang Qing  Hidenori Negoro  Keiichi Kumasawa  Kumiko Temma-Asano  Tateki Tsutsui  Katsuhiko Nishimori  Tadashi Kimura
Affiliation:Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan;;
Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai, Japan
Abstract:Problem  The oxytocin (OT)–oxytocin receptor (OTR) system plays an important role in mammalian parturition. However, we found OTR-deficient (OTRKO) mice are fertile and deliver at term without birth defects, thus alternative pathways inducing parturition can be hypothesized.
Methods of study  We tested the gene expression profile of OTRKO mice using suppressive subtractive hybridization, and focused on the calcineurin/nuclear factor of activated T cells (NFAT) pathway. We examined the expression and localization of this pathway in mouse parturition.
Results  Calcineurin and NFATc1 were detected in the decidua of pregnant uteri at term using immunohistochemistry (IHC). We identified higher activation levels of NFATc1 in wild type (WT) than in OTRKO mice and increased calcineurin A and NFATc1 mRNA levels during pregnancy. Moreover, injection of FK506, the inhibitor of this pathway, prolonged the delivery of the first pup.
Conclusion  Our findings suggested that the calcineurin/NFAT pathway might play a substantial role in initiation of labor.
Keywords:FK506    oxytocin    oxytocin receptor-deficient mouse    suppression subtractive hybridization
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