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

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-kappaB pathway, tumor necrosis factor-alpha and interleukin 1beta all increased in placental tissues after labor. Stabilization of hypoxia-inducible factor-1alpha 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.

Regulation of vascular growth and function in the human placenta

“…We have observed the same distribution of oxidative stress in placentas from uncomplicated pregnancies following labour and vaginal delivery, while it is absent from those delivered by caesarean section (Fig. 4; Cindrova-Davies et al 2007).…”

Perfusion of human placenta with hemoglobin introduces preeclampsia-like injuries that are prevented by α1-microglobulin

“…Recently, it was shown that labor initiates oxidative stress which, depending on length and intensity, varies with the lowest degree of stress found in placental tissue from elective cesarean section [41]. As far as the gene profile is concerned, there apparently is no unanimous opinion [42].…”

Evidence of Placental Translation Inhibition and Endoplasmic Reticulum Stress in the Etiology of Human Intrauterine Growth Restriction

“…Although preterm placentas would match the gestational age of the IUGR and PEϩIUGR placentas, they are commonly associated with pathological processes 54,55 and so there is considerable doubt as to whether they are truly normal. In addition, our previous results have shown that labor induces significant cellular stress within the placenta, 56 and nonlabored preterm healthy placentas delivered by elective caesarean section are almost impossible to obtain. On the other hand, we did not observe any correlation between gestational age and any of the data presented (Figure 1).…”