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Dose-Dependent Effects of Meloxicam Administration on Cyclooxygenase-1 and Cyclooxygenase-2 Protein Expression in Intrauterine Tissues and Fetal Tissues of a Sheep Model of Preterm Labor

Research Centre for Women's and Infant's Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

Catherine A. Scott, MSc

Research Centre for Women's and Infant's Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

Charlene Small

Research Centre for Women's and Infant's Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

S. Lee Adamson, PhD

Research Centre for Women's and Infant's Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada, Department of Physiology, University of Toronto, Toronto, Ontario, Canada

Dan Rurak, PhD

BC Research Institute for Children's & Women's Health, Vancouver, British Columbia, Canada, Department of Obstetrics and Gynecology, University of British Columbia,Vancouver, British Columbia, Canada

John R. Challis, PhD

Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada, Department of Physiology, University of Toronto, Toronto, Ontario, Canada

Stephen J. Lye, PhD

Research Centre for Women's and Infant's Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada, Department of Physiology, University of Toronto, Toronto, Ontario, Canada, lye{at}mshri.on.ca

Meloxicam (MEL), a cyclooxygenase (COX)—2 inhibitor, decreases prostaglandin production and blocks preterm labor in sheep. The objective of this study is to investigate MEL dosage regimens on COX-1, COX-2, and prostaglandin dehydrogenase (PGDH) expression in ovine intrauterine and fetal tissues. Animals in preterm labor received maternal infusions of saline or MEL at maintained high or graded doses (study 1) or acute graded doses (study 2). MEL blocked preterm labor. In study 1, MEL decreased COX-2 expression in the endometrium, myometrium, and amnion but not placenta or fetal tissues. In study 2, COX-2 expression was unchanged. COX-1/PGDH expression was unaffected. While MEL is an effective tocolytic, reductions in COX-2 protein occurred only with maintained MEL exposure. MEL effects are tissue specific and do not affect COX-1 or PGDH expression. Maternal MEL does not affect fetal COX expression in the sheep, possibly contributing to its lack of fetal side effects.

Key Words: Cyclooxygenase enzyme • preterm labor • pregnant sheep model • meloxicam • prostaglandins.

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