The Study of Cyclooxygenase 2 in Human Decidua of Preeclampsia1

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Abstract

Preeclampsia (PE), a pregnancy-specific disorder characterized by hypertension and proteinuria beginning after 20 wk of pregnancy, is a major cause of maternal and fetal morbidity and mortality. Delivery of the placenta reverses the immediate clinical manifestations and remains the only reliable treatment for PE. Up to now, the causes of PE are not entirely clear. Human cyclooxygenase 2 (COX2, encoded byPTGS2) is a highly inducible enzyme and regulates inflammation, differentiation, mitogenesis, and angiogenesis. COX2 deficiency affects all stages of early pregnancy and leads to various impairments. We hypothesized that COX2 had a role in the occurrence of PE and investigated its expression and function. We found that the expression of COX2 in decidual tissues of PE was significantly lower compared to that of the normal pregnancy. After decidualization stimulation with N6, 2′-O-dibutyryl-cAMP and medroxyprogesterone 17-acetate of human endometrial stromal cells, the expression of COX2, decidualization marker molecules prolactin (PRL) and insulinlike growth factor binding protein 1 (IGFBP1) increased significantly. This augmentation was time dependent relative to decidualization. WhenPTGS2was depleted, the decidualization was compromised, based on changes in morphology and in decidualization markers. We found that the mRNA and protein levels of vascular endothelial growth factor (VEGF) decreased markedly whenPTGS2was knocked down, providing a potential mechanism for decidual impairment. This was consistent with the decrease in mRNA and protein in decidual tissues of PE relative to normal tissues. Our results suggest that COX2 plays a vital role in human decidualization and that its decreased expression jeopardizes decidualization and vascularization of the endometrial stroma; it may be a significant factor in the occurrence of PE.

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