Multi-omic brain and behavioral correlates of cell-free fetal DNA methylation in macaque maternal obesity models.

Autor: Laufer BI; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, 95616, USA.; UC Davis Genome Center, University of California, Davis, CA, 95616, USA.; MIND Institute, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.; Department of OMNI Bioinformatics, Genentech, Inc., South San Francisco, CA, 94080, USA., Hasegawa Y; Department of Food Science and Technology, University of California Davis, Davis, CA, 95616, USA., Zhang Z; Department of Food Science and Technology, University of California Davis, Davis, CA, 95616, USA., Hogrefe CE; California National Primate Research Center, University of California Davis, Davis, CA, 95616, USA., Del Rosso LA; California National Primate Research Center, University of California Davis, Davis, CA, 95616, USA., Haapanen L; MIND Institute, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA., Hwang H; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, 95616, USA.; UC Davis Genome Center, University of California, Davis, CA, 95616, USA.; MIND Institute, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA., Bauman MD; MIND Institute, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.; California National Primate Research Center, University of California Davis, Davis, CA, 95616, USA.; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California Davis, Davis, CA, 95616, USA.; Perinatal Origins of Disparities Center, University of California Davis, Davis, CA, 95616, USA., Van de Water J; Perinatal Origins of Disparities Center, University of California Davis, Davis, CA, 95616, USA.; Department of Internal Medicine, University of California Davis, Davis, CA, 95616, USA., Taha AY; Department of Food Science and Technology, University of California Davis, Davis, CA, 95616, USA., Slupsky CM; Department of Food Science and Technology, University of California Davis, Davis, CA, 95616, USA.; Perinatal Origins of Disparities Center, University of California Davis, Davis, CA, 95616, USA.; Department of Nutrition, University of California Davis, Davis, CA, 95616, USA., Golub MS; California National Primate Research Center, University of California Davis, Davis, CA, 95616, USA., Capitanio JP; California National Primate Research Center, University of California Davis, Davis, CA, 95616, USA.; Department of Psychology, University of California Davis, Davis, CA, 95616, USA., VandeVoort CA; California National Primate Research Center, University of California Davis, Davis, CA, 95616, USA.; Department of Obstetrics and Gynecology, School of Medicine, University of California Davis, Davis, CA, 95616, USA., Walker CK; MIND Institute, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.; California National Primate Research Center, University of California Davis, Davis, CA, 95616, USA.; Perinatal Origins of Disparities Center, University of California Davis, Davis, CA, 95616, USA.; Department of Obstetrics and Gynecology, School of Medicine, University of California Davis, Davis, CA, 95616, USA., LaSalle JM; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, 95616, USA. jmlasalle@ucdavis.edu.; UC Davis Genome Center, University of California, Davis, CA, 95616, USA. jmlasalle@ucdavis.edu.; MIND Institute, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA. jmlasalle@ucdavis.edu.; Perinatal Origins of Disparities Center, University of California Davis, Davis, CA, 95616, USA. jmlasalle@ucdavis.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Sep 21; Vol. 13 (1), pp. 5538. Date of Electronic Publication: 2022 Sep 21.
DOI: 10.1038/s41467-022-33162-7
Abstrakt: Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. We conclude that in this model, maternal obesity was associated with changes in the infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic factors.
(© 2022. The Author(s).)
Databáze: MEDLINE
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