Maternal Circulating MiRNAs That Predict Infant FASD Outcomes Influence Placental Maturation
| Autor: | Tseng, Alexander M., Mahnke, Amanda H., Wells, Alan B., Salem, Nihal A., Allan, Andrea M., Roberts, Victoria H.J., Newman, Natali, Walter, Nicole A.R., Kroenke, Christopher D., Grant, Kathleen A., Akison, Lisa K., Moritz, Karen M., Chambers, Christina D., Miranda, Rajesh C. |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Pregnancy 030219 obstetrics & reproductive medicine Cell growth Trophoblast Placental insufficiency Biology medicine.disease 3. Good health Andrology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Placenta microRNA embryonic structures medicine Endocrine system Gestation 030304 developmental biology |
| DOI: | 10.1101/409854 |
| Popis: | Prenatal Alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, though the linking causal mechanisms are unclear. We previously identified 11 gestationally-elevated maternal circulating miRNAs that predicted infant growth deficits following PAE. Here, we investigated whether theseHEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial-mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time, that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and thatHEamiRNAs collectively, but not individually, mediate placental EMT inhibition.HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intra-vascular administration of the pooled murine-expressedHEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited expression of pro-EMT transcripts in placenta. Our data suggests thatHEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.SummaryMaternal gestational circulating microRNAs, predictive of adverse infant outcomes including growth deficits, following prenatal alcohol exposure, contribute to placental pathology by impairing the EMT pathway in trophoblasts. |
| Databáze: | OpenAIRE |
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