Molecular pathways regulating contractility in rat uterus through late gestation and parturition.
OBJECTIVE
Endogenous uterine agonists can activate numerous signaling pathways to effect increased force. Our objective was to assess expression of key constituents of these pathways, in alliance with contractile function, through late gestation and during term and preterm labor.


METHODS
Using myography, we measured the response to 3 agonists compared with depolarization alone (K(+), 124 mEq/L) and calculated agonist/depolarization ratio. We measured gene expression using quantitative reverse transcription-polymerase chain reaction.


RESULTS
Contractile responsiveness to depolarization alone, oxytocin, or endothelin-1 increased during pregnancy compared with nonpregnant animals. The agonist/depolarization ratio did not change during uterine activation or parturition. Inhibition of rhoA-associated kinase decreased responses to oxytocin in all tissues, but significantly more during uterine activation. Expression of rhoA and rhoA-associated kinase was increased significantly in active labor at term or preterm.


CONCLUSIONS
The rhoA/rhoA-associated kinase pathway is a key regulator of uterine activation during labor and may be a useful target for the prevention of spontaneous preterm birth.
Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, United Kingdom.
Michael J
MJ
Taggart
Patrice
P
Arthur
Barbara
B
Zielnik
Bryan F
BF
Mitchell
D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D023421:Models, Animal; D009213:Myography; D010121:Oxytocin / Q000378:metabolism; D036801:Parturition / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011247:Pregnancy / Q000502:physiology*; D047928:Premature Birth / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014590:Uterine Contraction / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D019332:Endothelin-1; D010121:Oxytocin; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D011188:Potassium