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15-Hydroxyprostaglandin Dehydrogenase: Implications in Preterm Labor with and without Ascending Infection¹

Department of Obstetrics and Gynecology, Leiden University Hospital (C.A.V.M., M.J.N.C.K.), Leiden, The Netherlands; and the Department of Obstetrics and Gynecology, Medical Research Council Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St. Joseph’s Health Center, University of Western Ontario (S.G.M., M.M.R., A.B., J.R.G.C.), London; and the Department of Physiology, University of Toronto (S.G.M., J.R.G.C.), Toronto, Ontario, Canada

Address all correspondence and requests for reprints to: Dr. J. R. G. Challis, Department of Physiology, Faculty of Medicine, University of Toronto, Medical Science Building, 1 King’s College Circle, Toronto, Ontario, Canada M5S 1A8.

There is evidence that intrauterine infection, which stimulates PG synthesis may play a role in the pathogenesis of some preterm labor. Local tissue concentrations of PGs are controlled not only by the rate of synthesis, but also by catabolism, which is regulated by 15-hydroxyprostaglandin dehydrogenase (PGDH). We hypothesized that a decrease of PGDH activity could contribute to an increase in PG output at the time of preterm labor (PTL) especially in association with infection. We measured PGDH activity with a zero order kinetic enzymatic assay, PGDH messenger ribonucleic acid by in situ hybridization and PGDH distribution and localization with immunohistochemistry in human placenta and fetal membranes from women at term before (n = 10) or after (n = 16) labor compared to preterm labor at less than 36 weeks without (n = 16) and with (n = 11) chorioamnionitis. PGDH activity in chorion was significantly lower in PTL than at term and was further reduced when PTL was associated with inflammation. Immunoreactive PGDH and PGDH messenger ribonucleic acid localized predominantly to chorionic trophoblasts at term and were reduced in PTL women with or without infection. These effects were not observed in the placenta. Loss of PGDH with infection was associated with infiltration of chorion by polymorphonuclear leukocytes, resulting in a compromised structural integrity, although the amniotic epithelium was generally intact. We conclude that a reduction in PGDH in the human fetal membranes may occur in some cases of preterm labor and may contribute to an increase in net PG accumulation and drive to myometrial contractility.

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