Abstract
PurposeSeveral 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.MethodsHuman 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.ResultsMyometrial 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.ConclusionsThe human myometrium responds to short-term exposure (48 h) to high glucose concentrations by regulating the expression of miRNAs, IGF1R and its downstream targets.
Highlights
The myometrium comprises the contractile unit of the uterus, in which bundles of smooth muscle cells are organized in two distinct layers supported by connective tissue inbetween [1]
Despite the importance of the myometrium for reproduction and the impairments promoted by diabetes on it, surprisingly little is known on how high glucose affects this compartment
We demonstrate that the myometrium is sensitive to short-term exposure (48 h) of high glucose concentration
Summary
The myometrium comprises the contractile unit of the uterus, in which bundles of smooth muscle cells are organized in two distinct layers supported by connective tissue inbetween [1]. Myometrial alterations are associated with reproductive disorders [5]. This is especially relevant in the context of diabetes, where both preterm deliveries and cesarean rates are considerably higher due to labor dysfunctions [6,7,8]. While insulin deficiency caused by beta-cell destruction characterizes type 1 diabetes, type 2 diabetes is promoted by impairment of insulin actions due to alterations in insulin receptor signaling, a phenomenon known as insulin resistance. Hyperglycemia and associated metabolic disarrangements are detrimental to cells leading to tissue and organ dysfunctions [10]
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