Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany.
Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Arch Gynecol Obstet. 2021 Jun;303(6):1513-1522. doi: 10.1007/s00404-020-05940-5. Epub 2021 Feb 11.
Several roles are attributed to the myometrium including sperm and embryo transport, menstrual discharge, control of uterine blood flow, and labor. Although being a target of diabetes complications, the influence of high glucose on this compartment has been poorly investigated. Both miRNAs and IGF1R are associated with diabetic complications in different tissues. Herein, we examined the effects of high glucose on the expression of miRNAs and IGF1R signaling pathway in the human myometrium.
Human myometrial explants were cultivated for 48 h under either high or low glucose conditions. Thereafter, the conditioned medium was collected for biochemical analyses and the myometrial samples were processed for histological examination as well as miRNA and mRNA expression profiling by qPCR.
Myometrial structure and morphology were well preserved after 48 h of cultivation in both high and low glucose conditions. Levels of lactate, creatinine, LDH and estrogen in the supernatant were similar between groups. An explorative screening by qPCR arrays revealed that 6 out of 754 investigated miRNAs were differentially expressed in the high glucose group. Data validation by single qPCR assays confirmed diminished expression of miR-215-5p and miR-296-5p, and also revealed reduced miR-497-3p levels. Accordingly, mRNA levels of IGF1R and its downstream mediators FOXO3 and PDCD4, which are potentially targeted by miR-497-3p, were elevated under high glucose conditions. In contrast, mRNA expression of IGF1, PTEN, and GLUT1 was unchanged.
The human myometrium responds to short-term exposure (48 h) to high glucose concentrations by regulating the expression of miRNAs, IGF1R and its downstream targets.
子宫肌层具有多种功能，包括输送精子和胚胎、月经排出、控制子宫血流和分娩。尽管它是糖尿病并发症的靶器官，但高血糖对该组织的影响尚未得到充分研究。miRNA 和 IGF1R 均与不同组织中的糖尿病并发症有关。在此，我们研究了高葡萄糖对人子宫肌层中 miRNA 和 IGF1R 信号通路表达的影响。
将人子宫肌层标本在高糖或低糖条件下培养 48 小时。然后收集条件培养基进行生化分析，并对子宫肌层标本进行组织学检查以及通过 qPCR 进行 miRNA 和 mRNA 表达谱分析。
在高糖和低糖条件下培养 48 小时后，子宫肌层的结构和形态均得到良好保存。上清液中的乳酸、肌酐、LDH 和雌激素水平在各组间相似。通过 qPCR 芯片进行的探索性筛选显示，在高糖组中，754 个研究的 miRNA 中有 6 个表达不同。通过单 qPCR 检测进行的数据验证证实，miR-215-5p 和 miR-296-5p 的表达减少，并且 miR-497-3p 的水平也降低。相应地，IGF1R 及其下游介质 FOXO3 和 PDCD4 的 mRNA 水平在高糖条件下升高，而 IGF1、PTEN 和 GLUT1 的 mRNA 表达不变。
人子宫肌层对短期（48 小时）暴露于高葡萄糖浓度的反应是通过调节 miRNA、IGF1R 及其下游靶标的表达来实现的。
