Abstract
Background
Exposure to diabetes in utero influences future metabolic health of the offspring. MicroRNAs (miRNA) are small noncoding RNAs that may contribute mechanistically to the effects on offspring imparted by diabetes mellitus (DM) during pregnancy. We hypothesized that exposure to DM during pregnancy influences select miRNAs in fetal circulation, in human umbilical vein endothelial cells (HUVEC), and placenta.
Methods
miRNA abundance was quantified using real-time PCR from RNA isolated from umbilical cord serum exosomes, HUVEC, and placenta exposed to diabetes or normoglycemia during pregnancy. The abundance of each of these miRNAs was determined by comparison to a known standard and the relative expression assessed using the 2−ΔΔCt method. Multivariable regression models examined the associations between exposure to diabetes during pregnancy and miRNA expression.
Results
miR-126-3p was highly abundant in fetal circulation, HUVEC, and placenta. Diabetes exposure during pregnancy resulted in lower expression of miR-148a-3p and miR-29a-3p in the HUVEC. In the placenta, for miR-126-3p, there was a differential effect of DM by birth weight between DM versus control group, expression being lower at the lower birth weight, however not different at the higher birth weight.
Conclusion
Exposure to DM during pregnancy alters miRNA expression in the offspring in a tissue-specific manner.
Impact
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miRNAs are differentially expressed in fetal tissues from offspring exposed to in utero diabetes mellitus compared to those who were not exposed.
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miRNA expression differs among tissue types (human umbilical vein endothelial cells, placenta and circulation exosomes) and response to diabetes exposure varies according to tissue of origin.
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miRNA expression is also affected by maternal and infant characteristics such as infant birth weight, infant sex, maternal age, and maternal BMI.
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miRNAs might be one of the potential mechanisms by which offspring’s future metabolic status may be influenced by maternal diabetes mellitus.
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Acknowledgements
We thank our study participants. Funding was received from NIH 1K23DK106533-01A1, Endocrine Fellow Foundation Grant, Children Hospital Foundation Fellow Research Award.
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K.B.S. contributed to experimental design, sample analysis, data analysis, interpretation, and manuscript preparation. S.D.C. was involved in experimental design, data analysis, interpretation, and manuscript preparation. A.M.T. assisted with sample analysis, data analysis, and manuscript preparation. D.E.B. provided statistical analyses for the miRNA experiments and assisted in manuscript preparation. J.B.T. was involved in experimental design, sample analysis, data analysis, interpretation, and manuscript preparation. All authors gave their final approval of this paper for publication.
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Shah, K.B., Chernausek, S.D., Teague, A.M. et al. Maternal diabetes alters microRNA expression in fetal exosomes, human umbilical vein endothelial cells and placenta. Pediatr Res 89, 1157–1163 (2021). https://doi.org/10.1038/s41390-020-1060-x
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DOI: https://doi.org/10.1038/s41390-020-1060-x
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