Reciprocal expression of peroxisome proliferator-activated receptor-γ and cyclooxygenase-2 in human term parturition

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Abstract

Objective

The objective of this study was to test the hypothesis that peroxisome proliferator activated receptor-γ (PPAR-γ) is expressed in intrauterine tissues before active term human parturition, and that its repression is associated with up-regulation of cyclooxygenase-2 (COX-2).

Study Design

Specimens were collected from women with term singleton pregnancies after spontaneous labor or cesarean section before labor, prepared for immunoblot and immunohistochemical analysis, and probed for PPAR-γ or COX-2.

Results

PPAR-γ expression was prominent in fetal membranes and placenta before active labor. After labor, PPAR-γ expression was significantly reduced in fetal membranes, but not in placenta. The ratio of COX-2:PPAR-γ was significantly elevated in fetal membranes with labor. PPAR-γ immunostaining was prominent in syncytiotrophoblast, extravillous cytotrophoblasts, and cells of the amnion and chorion. COX-2 immunostaining was abundant in the amnion and rare in the placenta.

Conclusion

PPAR-γ is highly expressed in term intrauterine tissues. In fetal membranes, PPAR-γ levels are reduced once active labor commences, coincidental with a relative increase in COX-2 expression.

Section snippets

Subject recruitment

All procedures were conducted under a protocol approved by the Institutional Review Board of The Ohio State University Medical Center, and informed consent was obtained from all women. Placentas with attached fetal membranes were collected from women with uncomplicated singleton pregnancies following term (≥37 weeks of gestation), spontaneous labor (SL), or cesarean section (CS) without labor. The tissues were transported to our laboratory within 30 minutes following delivery in 0.9% NaCl.

COX-2 and PPAR-γ are reciprocally expressed in term fetal membranes after labor

The mean gestational age at delivery for the TL group was 39.6 weeks (range, 38.4-41.1 weeks), which was similar to that for the CS group (38.9 weeks; range, 37.1-40.3 weeks).

Other clinical and demographic data did not differ appreciably between the groups (Table). Women in the TL group were recruited after presenting with regular uterine contractions accompanied by changes in cervical dilation or effacement. Women undergoing induction of labor were excluded, although women undergoing

Comment

The observation of increased levels of inflammatory cytokines (interleukin-1, interleukin-6, interleukin-8, and tumor necrosis factor) within intrauterine tissues after labor indicates that inflammation plays a significant role in term human parturition.22 As autocrine and paracrine mediators, these cytokines in turn stimulate uterotonic PG formation, which is achieved primarily via de novo COX-2 expression.1., 2., 3. PGs, in turn, facilitate cervical maturation and myometrial contractility.3

Acknowledgements

We thank Valerie J. Curry, RN, for assistance in patient enrollment and specimen collection. We additionally thank Peter Zimmerman (The Ohio State University, Department of Pathology) and Susan Jones (The Ohio State University Histology Core Facility) for excellent technical support. This work was performed while Dr Lisa Dunn-Albanese was a Fellow in maternal-fetal medicine at The Ohio State University. This work was supported by National Institutes of Health HD35881 and The Ohio State

References (29)

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This work was supported by National Institutes of Health HD35881 and The Ohio State University Perinatal Research and Development Fund.

Dr Dunn-Albanese and Dr Ackerman contributed equally to this work.

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