Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

CiteULike is a free service for managing and discovering scholarly references - click here to get started.

Sign In to gain access to subscriptions and/or personal tools.
Reproductive Sciences
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Rac, V. E.
Right arrow Articles by Lye, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rac, V. E.
Right arrow Articles by Scott, C. A.
Right arrow Articles by Small, C.
Right arrow Articles by Lee Adamson, S.
Right arrow Articles by Rurak, D.
Right arrow Articles by Challis, J. R.
Right arrow Articles by Lye, S. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

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

Valeria E. Rac, MD, 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

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.

References

  • Joseph KS, Kramer MS, Marcoux S., Ohlsson A., Wu Wen S., Allen A. Determinants of preterm birth rates in Canada from 1981 through 1983 and from 1992 through 1994. N Engl J Med. 1998;339:1434-1439.[Abstract/Free Full Text]
  • Moutquin JM, Lalonde A. The cost of prematurity in Canada. Paper presented at: Preterm Birth Prevention Conference; April 24-25, 1998; Ottawa, Canada.
  • Lye SJ, Ou CW, Teoh TG, Stevens Y., Casper R. The molecular basis of labor and tocolysis. Fetal Maternal Med Rev. 1998;10:121-136.[CrossRef]
  • Challis JR, Lye SJ, Gibb W., Whittle W., Patel F., Alfaidy N. Understanding preterm labor. Ann N Y Acad Sci. 2001; 943:225-234.[Web of Science][Medline] [Order article via Infotrieve]
  • Challis JR, Sloboda DM, Alfaidy N. et al. Prostaglandins and mechanisms of preterm birth. Reproduction. 2002;124:1-17.[Abstract]
  • Olson DM The role of prostaglandins in the initiation of parturition. Best Pract Res Clin Obstet Gynaecol. 2003;17:717-730.[CrossRef][Medline] [Order article via Infotrieve]
  • Smith WL, De Witt DL, Garavito RM Cyclooxygenases: structural, cellular and molecular biology. Annu Rev Biochem. 2000;69:145-182.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Yasojima K., Schwab C., McGeer EG, McGeer PL Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs. Brain Res. 1999; 830:226-236.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kniss DA Cyclooxygenases in reproductive medicine and biology. J Soc Gynecol Investig. 1999;6:285-292.[Web of Science][Medline] [Order article via Infotrieve]
  • Higby K., Xenakis EMJ, Pauerstein CJ Do tocolytic agents stop preterm labor? A critical and comprehensive review of efficacy and safety. Am J Obstet Gynecol. 1993;168:1247-1259.[Web of Science][Medline] [Order article via Infotrieve]
  • Norton ME, Merrill JD, Cooper BAB, Kuller JA, Clyman RI Neonatal complications after the administration of indomethacin for preterm labor. N Engl J Med. 1993;329:1602-1607.[Abstract/Free Full Text]
  • Major CA, Lewis DF, Harding JA, Porto MA, Garite TJ Tocolysis with indomethacin increases the incidence of necrotizing enterocolitis in the low birth-weight neonate. Am J Obstet Gynecol. 1994;170:102-106.[Web of Science][Medline] [Order article via Infotrieve]
  • Panter KR, Hannah ME, Amankwah KS, Ohlsson A., Jefferies AL, Farine D. The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial. Br J Obstet Gynaecol. 1999;106:467-473.[Web of Science][Medline] [Order article via Infotrieve]
  • Sawdy R., Slater D., Fisk N., Edmonds DK, Bennett P. Use of a cyclo-oxygenase type-2- selective non-steroidal antiinflammatory agent to prevent preterm delivery. Lancet. 1997; 350:265-266.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • McKeown KJ, Challis JR, Small C., et al.Altered fetal pituitary-adrenal function in the ovine fetus treated with RU486 and meloxicam, an inhibitor of prostaglandin synthase-II. Biol Reprod. 2000; 63:1899-1904.[Abstract/Free Full Text]
  • Rac VE, Small C., Scott CA, et al. Meloxicam effectively inhibits preterm labor uterine contractions in a chronically catheterized pregnant sheep model: impact on fetal blood flow and fetal/maternal physiologic parameters. Am J Obstet Gynecol. 2006;195:528-534.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Wu WX, Unno N., Ma XH, Nathanielsz PW Inhibition of prostaglandin production by nimesulide is accompanied by changes in expression of the cassette of uterine labor-related genes in pregnant sheep. Endocrinology. 1998;139:3096-3103.[Abstract/Free Full Text]
  • Frenkian M., Segond N., Pidoux E., Cohen R., Jullienne A. Indomethacin, a cox inhibitor, enhances 15-PGDH and decreases human tumoral C cells proliferation. Prostaglandins Other Lipid Mediat. 2001;65:11-20.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hirst JJ, Teixeira FJ, Zakar T., Olson DM Prostaglandin H synthase-2 expression increases in human gestational tissues with spontaneous labour onset. Reprod Fertil Dev. 1995;7:633-637.[CrossRef][Medline] [Order article via Infotrieve]
  • Gibb W., Matthews SG, Challis JR Localization and developmental changes in prostaglandin H synthase (PGHS) and PGHS messenger ribonucleic acid in ovine placenta throughout gestation. Biol Reprod. 1996;54:654-659.[Abstract]
  • Kawai S. Cyclooxygenase selectivity and the risk of gastro-intestinal complications of various non-steroidal antiinflammatory drugs: a clinical consideration. Inflamm Res. 1998;47(suppl 2):S102-S106.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • McLaren WJ,Young IR, Rice GE Localisation and temporal changes in prostaglandin G/H synthase-1 and -2 content in ovine intrauterine tissues in relation to glucorticoid-induced and spontaneous labour. J Endocrinol. 2000;165:399-410.[Abstract]
  • Palliser HK, Hirst JJ, Rice GE, et al. Labour-associated regulation of prostaglandin E and F synthesis and action in the ovine amnion and cervix. J Soc Gynecol Investig. 2006;13:19-24.[Web of Science][Medline] [Order article via Infotrieve]
  • Gyomorey S., Lye SJ, Gibb W., Challis JR Fetal-to-maternal progression of prostaglandin H(2) synthase-2 expression in ovine intrauterine tissues during the course of labor. Biol Reprod. 2000;62:797-805.[Abstract/Free Full Text]
  • Wu XW, Xiao HM, Nathanielsz PW Tissue-specific ontogenic expression of prostaglandin H synthase 2 in the ovine myometrium, endometrium, and placenta during late gestation and at spontaneous term labor. Am J Obstet Gynecol. 1999; 181:1512-1519.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hawkey CJ COX-2 inhibitors. Lancet. 1999;353:307-314.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Tsai SJ,Wiltbank MC Prostaglandin F2alpha induces expression of prostaglandin G/H synthase-2 in the ovine corpus luteum: a potential positive feedback loop during luteolysis. Biol Reprod. 1997;57:1016-1022.[Abstract]
  • Rurak D., Hu L., McKeown K., et al. Inhibition RU486-induced preterm labor in sheep with meloxicam: drug concentration versus effects relationships. Society for Gynecologic Investigation, Annual Meeting, Toronto, ON, Canada, March 2001. J Soc Gynecol Investig. 2001;8(suppl):277A.
  • Faber J., Thornburg KL Placental Physiology. New York, NY: Raven Press; 1983.
  • Okita RT, Okita JR Prostaglandin metabolizing enzymes during pregnancy: characterization of NAD+-dependent prostaglandin dehydrogenase, carbonyl reductase, and cytochrome P450-dependent prostaglandin omega-hydroxylase. Crit Rev Biochem Mol Biol. 1996;31:101-126.[Web of Science][Medline] [Order article via Infotrieve]

Reproductive Sciences, Vol. 14, No. 8, 750-764 (2007)
DOI: 10.1177/1933719107309042
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Rac, V. E.
Right arrow Articles by Lye, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rac, V. E.
Right arrow Articles by Scott, C. A.
Right arrow Articles by Small, C.
Right arrow Articles by Lee Adamson, S.
Right arrow Articles by Rurak, D.
Right arrow Articles by Challis, J. R.
Right arrow Articles by Lye, S. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?