Calcineurin/NFAT pathway: a novel regulator of parturition.
OBJECTIVE
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
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.


CONCLUSIONS
Our findings suggested that the calcineurin/NFAT pathway might play a substantial role in initiation of labor.
Tabata
Chisa
C
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan.
Ogita
Kazuhide
K
Sato
Keisuke
K
Nakamura
Hitomi
H
Qing
Zhang
Z
Negoro
Hidenori
H
Kumasawa
Keiichi
K
Temma-Asano
Kumiko
K
Tsutsui
Tateki
T
Nishimori
Katsuhiko
K
Kimura
Tadashi
T
D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010121:Oxytocin / Q000276:immunology; D036801:Parturition / Q000235:genetics / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000235:genetics; D015398:Signal Transduction; D016559:Tacrolimus / Q000494:pharmacology; D014599:Uterus / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D018045:Receptors, Oxytocin; D010121:Oxytocin; D019703:Calcineurin; D016559:Tacrolimus