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Prenatal Growth Patterns and Birthweight Are Associated With Differential DNA Methylation and Gene Expression of Cardiometabolic Risk Genes in Human Placentas: A Discovery-Based Approach.
Chen, Pao-Yang; Chu, Alison; Liao, Wen-Wei; Rubbi, Liudmilla; Janzen, Carla; Hsu, Fei-Man; Thamotharan, Shanthie; Ganguly, Amit; Lam, Larry; Montoya, Dennis; Pellegrini, Matteo; Devaskar, Sherin U.
Afiliação
  • Chen PY; 1 Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan.
  • Chu A; 2 Division of Neonatology and Developmental Biology, Department of Pediatrics, Neonatal Research Center of the UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Liao WW; 1 Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan.
  • Rubbi L; 3 Department of Molecular, Cell, and Developmental Biology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Janzen C; 4 Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Hsu FM; 1 Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan.
  • Thamotharan S; 2 Division of Neonatology and Developmental Biology, Department of Pediatrics, Neonatal Research Center of the UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Ganguly A; 2 Division of Neonatology and Developmental Biology, Department of Pediatrics, Neonatal Research Center of the UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Lam L; 3 Department of Molecular, Cell, and Developmental Biology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Montoya D; 3 Department of Molecular, Cell, and Developmental Biology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Pellegrini M; 3 Department of Molecular, Cell, and Developmental Biology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Devaskar SU; 2 Division of Neonatology and Developmental Biology, Department of Pediatrics, Neonatal Research Center of the UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Reprod Sci ; 25(4): 523-539, 2018 04.
Article em En | MEDLINE | ID: mdl-28693373
ABSTRACT
Inherent genetic programming and environmental factors affect fetal growth in utero. Epidemiologic data in growth-altered fetuses, either intrauterine growth restricted (IUGR) or large for gestational age (LGA), demonstrate that these newborns are at increased risk of cardiometabolic disease in adulthood. There is growing evidence that the in utero environment leads to epigenetic modification, contributing to eventual risk of developing heart disease or diabetes. In this study, we used reduced representation bisulfite sequencing to examine genome-wide DNA methylation variation in placental samples from offspring born IUGR, LGA, and appropriate for gestational age (AGA) and to identify differential methylation of genes important for conferring risk of cardiometabolic disease. We found that there were distinct methylation signatures for IUGR, LGA, and AGA groups and identified over 500 differentially methylated genes (DMGs) among these group comparisons. Functional and gene network analyses revealed expected relationships of DMGs to placental physiology and transport, but also identified novel pathways with biologic plausibility and potential clinical importance to cardiometabolic disease. Specific loci for DMGs of interest had methylation patterns that were strongly associated with anthropometric presentations. We further validated altered gene expression of these specific DMGs contributing to vascular and metabolic diseases (SLC36A1, PTPRN2, CASZ1, IL10), thereby establishing transcriptional effects toward assigning functional significance. Our results suggest that the gene expression and methylation state of the human placenta are related and sensitive to the intrauterine environment, as it affects fetal growth patterns. We speculate that these observed changes may affect risk for offspring in developing adult cardiometabolic disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Placenta / Peso ao Nascer / Metilação de DNA / Desenvolvimento Fetal Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Newborn / Pregnancy Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Placenta / Peso ao Nascer / Metilação de DNA / Desenvolvimento Fetal Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Newborn / Pregnancy Idioma: En Ano de publicação: 2018 Tipo de documento: Article