环氧化酶-2 信号通路功能障碍在不明原因复发性自然流产中的作用。

Role of cyclooxygenase-2 signaling pathway dysfunction in unexplained recurrent spontaneous abortion.

机构信息

Department of Obstetrics & Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

出版信息

Chin Med J (Engl). 2010 Jun;123(12):1543-7.

PMID:20819509

Abstract

BACKGROUND

Experimental evidence indicates that cyclooxygenase-2 (COX-2) plays a critical role in blastocyst implantation; however, little is known of the role of COX-2 in unexplained recurrent spontaneous abortion (URSA).

METHODS

We evaluated the expression level and potential signaling pathway of COX-2 in 30 cases of URSA who were excluded the abnormality of chromosomes, anatomy, endocrine, infectious, autoimmune diseases and in 30 normal pregnancies.

RESULTS

The mRNA and the protein expression level of COX-2 in the URSA group (-0.238 +/- 0.848, 0.368 +/- 0.089, respectively) were significantly lower than that in the control group (1.943 +/- 3.845, 1.046 +/- 0.108, respectively) (both, P < 0.01). The expression of prostaglandins PGF(2a), PGD(2), PGE(2), and PGI(2), in the URSA group ((2326.0 +/- 295.6) pg/ml, (2164.0 +/- 240.5) pg/ml, (238.7 +/- 26.4) pg/ml, (2337.0 +/- 263.0) pg/ml, respectively) were significantly lower than that in the control group ((3450.0 +/- 421.7) pg/ml, (3174.0 +/- 415.6) pg/ml, (323.5 +/- 43.8) pg/ml, (3623.0 +/- 460.4) pg/ml, respectively) (P < 0.05). The mRNA expression level of PPARbeta and RXRalpha (0.859 +/- 0.653, -0.172 +/- 0.752, respectively) in URSA group was significantly lower than that in the control group (1.554 +/- 1.735, 0.777 +/- 2.482, respectively) (both P< 0.05). The mRNA and protein expression levels of vascular endothelial growth factor-A (VEGF-A) in the URSA group (2.010 +/- 1.522, 0.35 +/- 0.46) was significantly lower than that in the control group (4.569 +/- 2.430, 0.750 +/- 0.350) (both P < 0.05).

CONCLUSIONS

COX-2 and the COX-2-derived PGI(2) signaling pathway possibly play an important role in successful embryo implantation, and their decreased expression may result in URSA. The decreased expression may influence the expression of VEGF-A which interferes with placental angiogenesis causing failure of embryo implantation, leading to spontaneous abortion.

摘要

背景

实验证据表明环氧化酶-2（COX-2）在胚泡着床中起着关键作用；然而，关于 COX-2 在不明原因的复发性自然流产（URSA）中的作用知之甚少。

方法

我们评估了 30 例排除染色体、解剖、内分泌、感染、自身免疫性疾病异常的 URSA 患者和 30 例正常妊娠患者中 COX-2 的表达水平和潜在信号通路。

结果

URSA 组 COX-2 的 mRNA 和蛋白表达水平（分别为-0.238 +/- 0.848、0.368 +/- 0.089）明显低于对照组（分别为 1.943 +/- 3.845、1.046 +/- 0.108）（均 P < 0.01）。URSA 组前列腺素 PGF（2a）、PGD（2）、PGE（2）和 PGI（2）的表达水平分别为（2326.0 +/- 295.6）pg/ml、（2164.0 +/- 240.5）pg/ml、（238.7 +/- 26.4）pg/ml、（2337.0 +/- 263.0）pg/ml，明显低于对照组（分别为 3450.0 +/- 421.7）pg/ml、（3174.0 +/- 415.6）pg/ml、（323.5 +/- 43.8）pg/ml、（3623.0 +/- 460.4）pg/ml（均 P < 0.05）。URSA 组 PPARbeta 和 RXRalpha 的 mRNA 表达水平（分别为 0.859 +/- 0.653、-0.172 +/- 0.752）明显低于对照组（分别为 1.554 +/- 1.735、0.777 +/- 2.482）（均 P < 0.05）。URSA 组血管内皮生长因子-A（VEGF-A）的 mRNA 和蛋白表达水平（分别为 2.010 +/- 1.522、0.35 +/- 0.46）明显低于对照组（分别为 4.569 +/- 2.430、0.750 +/- 0.350）（均 P < 0.05）。