Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation
Copyright policy )Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation
Prenatal alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, although the linking causal mechanisms are unclear. We previously identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) 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 intravascular administration of the pooled murine-expressedHEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited the expression of pro-EMT transcripts in the placenta. Our data suggest thatHEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.
- THE UNIVERSITY OF QUEENSLAND Australia
- University of California, San Diego United States
- The University of Texas System United States
- Oregon Health & Science University United States
- UNIVERSITY OF CALIFORNIA SAN DIEGO
1301 Biochemistry, Biomedical and clinical sciences, Ethanol Exposure, Genetics and Molecular Biology (miscellaneous), Reproductive health and childbirth, Inbred C57BL, Rats, Sprague-Dawley, Alcohol Use and Health, Substance Misuse, Mice, Pregnancy, 1110 Plant Science, Infant Mortality, 2.1 Biological and endogenous factors, Aetiology, Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Research Articles, Pediatric, Tumor, Fetal Growth Retardation, Trophoblasts, Biological sciences, Alcoholism, 2307 Health, Trophoblast Invasion, Fetal Alcohol Spectrum Disorders, Prenatal Exposure Delayed Effects, Female, Microrna Expression Profiles, Biotechnology, Mesometrial Triangle, Epithelial-Mesenchymal Transition, Intellectual and Developmental Disabilities (IDD), Human Chorionic-Gonadotropin, 610, Alcohol Spectrum Disorders, Cell Line, 618, Cell Line, Tumor, Animals, Humans, Toxicology and Mutagenesis, Conditions Affecting the Embryonic and Fetal Periods, Circulating MicroRNA, Fetal Alcohol Spectrum Disorders (FASD), Cell Proliferation, E-Cadherin, Biomedical and Clinical Sciences, Ethanol, Contraception/Reproduction, Fetal-Growth Restriction, 500, Perinatal Period - Conditions Originating in Perinatal Period, Macaca mulatta, Placentation, Brain Disorders, Rats, Mice, Inbred C57BL, Reproductive Medicine, C19Mc Micrornas, Sprague-Dawley, 2303 Ecology
1301 Biochemistry, Biomedical and clinical sciences, Ethanol Exposure, Genetics and Molecular Biology (miscellaneous), Reproductive health and childbirth, Inbred C57BL, Rats, Sprague-Dawley, Alcohol Use and Health, Substance Misuse, Mice, Pregnancy, 1110 Plant Science, Infant Mortality, 2.1 Biological and endogenous factors, Aetiology, Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Research Articles, Pediatric, Tumor, Fetal Growth Retardation, Trophoblasts, Biological sciences, Alcoholism, 2307 Health, Trophoblast Invasion, Fetal Alcohol Spectrum Disorders, Prenatal Exposure Delayed Effects, Female, Microrna Expression Profiles, Biotechnology, Mesometrial Triangle, Epithelial-Mesenchymal Transition, Intellectual and Developmental Disabilities (IDD), Human Chorionic-Gonadotropin, 610, Alcohol Spectrum Disorders, Cell Line, 618, Cell Line, Tumor, Animals, Humans, Toxicology and Mutagenesis, Conditions Affecting the Embryonic and Fetal Periods, Circulating MicroRNA, Fetal Alcohol Spectrum Disorders (FASD), Cell Proliferation, E-Cadherin, Biomedical and Clinical Sciences, Ethanol, Contraception/Reproduction, Fetal-Growth Restriction, 500, Perinatal Period - Conditions Originating in Perinatal Period, Macaca mulatta, Placentation, Brain Disorders, Rats, Mice, Inbred C57BL, Reproductive Medicine, C19Mc Micrornas, Sprague-Dawley, 2303 Ecology
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).33 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!