Published online before print September 6, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070528

Accepted for publication July 17, 2007.

Article

Oxidative Stress, Gene Expression, and Protein Changes Induced in the Human Placenta during Labor

Tereza Cindrova-Davies^*, Hong-Wa Yung^*, Jemma Johns, Olivera Spasic-Boskovic^*, Svitlana Korolchuk^*, Eric Jauniaux, Graham J. Burton^*@, and D. Stephen Charnock-Jones

From the Departments of Physiology, Development, and Neuroscience,* and Obstetrics and Gynaecology, University of Cambridge, Cambridge; and the Academic Department of Obstetrics and Gynaecology, Royal Free and University College, London, United Kingdom

^@ To whom correspondence should be addressed. E-mail: gjb2{at}cam.ac.uk.

	Abstract

Malperfusion of the placenta has been implicated as a cause of oxidative stress in complications of human pregnancy, leading to release of proinflammatory cytokines and anti-angiogenic factors into the maternal circulation. Uterine contractions during labor are known to be associated with intermittent utero-placental perfusion. We therefore tested whether oxidative stress, proinflammatory cytokines, and angiogenic regulators were increased in placentas subjected to short (<5 hours) and long (>15 hours) labor compared with nonlabored controls delivered by cesarean section. In addition, broader changes in gene transcripts were assessed by microarray analysis. Oxidative stress, activation of the nuclear factor-B pathway, tumor necrosis factor- and interleukin 1 all increased in placental tissues after labor. Stabilization of hypoxia-inducible factor-1 and increased vascular endothelial growth factor soluble receptor-1 were also observed. By contrast, tissue levels of placenta growth factor decreased. Apoptosis was also activated in labored placentas. The magnitude of these changes related to the duration of labor. After labor, 55 gene transcripts were up-regulated and 35 down-regulated, and many of these changes were reflected at the protein level. In conclusion, labor is a powerful inducer of placental oxidative stress, inflammatory cytokines, and angiogenic regulators. Our findings are consistent with intermittent perfusion being the initiating cause. Placentas subjected to labor do not reflect the normal in vivo state at the molecular level.

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