Relationship between gene expression and function of uterotonic systems in the rat during gestation, uterine activation and both term and preterm labour
Relationship between gene expression and function of uterotonic systems in the rat during gestation, uterine activation and both term and preterm labour
复制标题
DOI：
10.1113/jphysiol.2008.164004
复制
发表时间：
2008-12-15
影响因子：
5.5
通讯作者：
Mitchell, Bryan F.
中科院分区：
文献类型：
--
作者：
Arthur, Patrice;Taggart, Michael J.;Mitchell, Bryan F.
我们已经记录了大鼠子宫中编码收缩相关蛋白的基因表达的妊娠和分娩（早产和足月）依赖性变化，并将这些变化与子宫收缩力的各种参数相关联。数据表明，妊娠第 20 天后，收缩激动系统的表达增加，同时松弛系统的表达减少。催产素 (OT)、其受体 (OTR)、前列腺素 (PG) H 合酶亚型 1 (PGHS-1) 和 PGF(2α) 受体 (FP) 的表达首先显着增加，然后是 PGHS-2、连接蛋白-43、内皮素-1 (ET-1) 和ET-1 受体亚型 ETA。与非妊娠动物相比，OTR 和 FP 的表达在妊娠中期显着降低。诱导型一氧化氮合酶 (iNOS) 的表达在妊娠期间显着增加，然后随着 OTR 和 FP 的增加而下降。子宫收缩力的功能变化伴随着基因表达的变化。 OT 是最有效的收缩兴奋剂。子宫带对 OT 的敏感性在妊娠早期和中期降低，然后在子宫激活时升高。黄体酮拮抗剂诱发的早产引起与正常足月相似的变化。分离的子宫内膜和子宫肌层中 mRNA 转录本的比较表明，子宫内膜是子宫肌层收缩力的重要调节因子，类似于内皮和血管平滑肌之间的关系。这种功能和基因表达分析的新颖结合为分娩生理学提供了新的见解。
We have documented gestation- and labour- (preterm and term) dependent changes in expression of genes encoding contraction associated proteins in the rat uterus and correlated these changes with various parameters of uterine contractility. The data demonstrate increased expression of contractile agonist systems concurrent with decreased expression of relaxant systems after gestational day 20. Significant increases in expression of oxytocin (OT), its receptor (OTR), prostaglandin (PG) H synthase isoform 1 (PGHS-1) and PGF(2 alpha) receptor (FP) occurred first, followed by increases in PGHS-2, connexin-43, endothelin-1 (ET-1) and the ET-1 receptor isoform ETA. Expression of OTR and FP was significantly reduced during mid-gestation compared to non-pregnant animals. Expression of inducible nitric oxide synthase (iNOS) increased significantly during pregnancy then decreased concurrently with the increase in OTR and FP. Functional changes in uterine contractility accompany changes in gene expression. OT was the most potent contractile stimulant. Sensitivity of uterine strips to OT was reduced in early and mid-pregnancy then increased at uterine activation. Progesterone antagonist-induced preterm labour caused changes similar to those at normal term. Comparison of mRNA transcripts in separated endometrium and myometrium suggested that the endometrium is an important regulator of myometrial contractility, analogous to the relationship between endothelium and vascular smooth muscle. This novel combination of functional and genetic expression analyses provides new insight into the physiology of parturition.