AbstractPrenatal 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.
Tseng, A. M., Mahnke, A. H., Wells, A. B., Salem, N. A., Allan, A. M., Roberts, V., ... CIFASD.
citation count
0
complete list of authors
Tseng, Alexander M||Mahnke, Amanda H||Wells, Alan B||Salem, Nihal A||Allan, Andrea M||Roberts, Victoria HJ||Newman, Natali||Walter, Nicole AR||Kroenke, Christopher D||Grant, Kathleen A||Akison, Lisa K||Moritz, Karen M||Chambers, Christina D||Miranda, Rajesh C
Book Title
bioRxiv
publication date
September 2018
Research
keywords
2 Aetiology
2.1 Biological And Endogenous Factors
3 Good Health And Well Being
32 Biomedical And Clinical Sciences
3215 Reproductive Medicine
Alcoholism, Alcohol Use And Health
Biotechnology
Brain Disorders
Conditions Affecting The Embryonic And Fetal Periods
Contraception/reproduction
Fetal Alcohol Spectrum Disorders (fasd)
Infant Mortality
Intellectual And Developmental Disabilities (idd)
Pediatric
Perinatal Period - Conditions Originating In Perinatal Period
Preterm, Low Birth Weight And Health Of The Newborn
