Influence of high glucose in the expression of miRNAs and IGF1R signaling pathway in human myometrial explants.

Autor: Favaro RR; Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany. rodolfo.favaro@med.uni-jena.de.; Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. rodolfo.favaro@med.uni-jena.de., Morales-Prieto DM; Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany., Herrmann J; Department of Gynecology and Obstetrics, Hufeland Klinikum, Weimar, Germany., Sonnemann J; Department of Pediatric Hematology and Oncology, Children's Clinic, Jena University Hospital, Jena, Germany., Schleussner E; Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany., Markert UR; Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany., Zorn TMT; Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Archives of gynecology and obstetrics [Arch Gynecol Obstet] 2021 Jun; Vol. 303 (6), pp. 1513-1522. Date of Electronic Publication: 2021 Feb 11.
DOI: 10.1007/s00404-020-05940-5
Abstrakt: Purpose: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Databáze: MEDLINE
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