Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders
Abstract Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-80734-y |
| _version_ | 1818752045187858432 |
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| author | Amanda H. Mahnke Georgios D. Sideridis Nihal A. Salem Alexander M. Tseng R. Colin Carter Neil C. Dodge Aniruddha B. Rathod Christopher D. Molteno Ernesta M. Meintjes Sandra W. Jacobson Rajesh C. Miranda Joseph L. Jacobson |
| author_facet | Amanda H. Mahnke Georgios D. Sideridis Nihal A. Salem Alexander M. Tseng R. Colin Carter Neil C. Dodge Aniruddha B. Rathod Christopher D. Molteno Ernesta M. Meintjes Sandra W. Jacobson Rajesh C. Miranda Joseph L. Jacobson |
| author_sort | Amanda H. Mahnke |
| collection | DOAJ |
| description | Abstract Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs ( ex miRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed ex miRNAs with clinically-relevant effect sizes (Cohen’s d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of ex miRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered ex miRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant ex miRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition. |
| first_indexed | 2024-12-18T04:45:13Z |
| format | Article |
| id | doaj.art-d5ca958dd8ca40a9a1ee3267343b567a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:45:13Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d5ca958dd8ca40a9a1ee3267343b567a2022-12-21T21:20:36ZengNature PortfolioScientific Reports2045-23222021-01-0111112310.1038/s41598-020-80734-yInfant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disordersAmanda H. Mahnke0Georgios D. Sideridis1Nihal A. Salem2Alexander M. Tseng3R. Colin Carter4Neil C. Dodge5Aniruddha B. Rathod6Christopher D. Molteno7Ernesta M. Meintjes8Sandra W. Jacobson9Rajesh C. Miranda10Joseph L. Jacobson11Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science CenterHarvard Medical School, Boston Children’s Hospital, Institutional Centers for Clinical and Translational ResearchDepartment of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science CenterDepartment of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science CenterDepartments of Pediatrics and Emergency Medicine, Institute of Human Nutrition, Columbia University Medical CenterDepartment of Psychiatry and Behavioral Neurosciences, Wayne State University School of MedicineDepartment of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science CenterDepartments of Human Biology and of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape TownDivision of Biomedical Engineering, Department of Human Biology, Faculty of Health Sciences, University of Cape TownDepartment of Psychiatry and Behavioral Neurosciences, Wayne State University School of MedicineDepartment of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science CenterDepartment of Psychiatry and Behavioral Neurosciences, Wayne State University School of MedicineAbstract Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs ( ex miRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed ex miRNAs with clinically-relevant effect sizes (Cohen’s d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of ex miRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered ex miRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant ex miRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition.https://doi.org/10.1038/s41598-020-80734-y |
| spellingShingle | Amanda H. Mahnke Georgios D. Sideridis Nihal A. Salem Alexander M. Tseng R. Colin Carter Neil C. Dodge Aniruddha B. Rathod Christopher D. Molteno Ernesta M. Meintjes Sandra W. Jacobson Rajesh C. Miranda Joseph L. Jacobson Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders Scientific Reports |
| title | Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders |
| title_full | Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders |
| title_fullStr | Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders |
| title_full_unstemmed | Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders |
| title_short | Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders |
| title_sort | infant circulating micrornas as biomarkers of effect in fetal alcohol spectrum disorders |
| url | https://doi.org/10.1038/s41598-020-80734-y |
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