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IN UTERO EXPOSURE TO CAFFEINE REDUCES DNA METHYLATION IN HUMAN MESENCHYMAL STEM CELLS
Author(s) -
Pregmon Emily,
Seat Mara,
Poulsen Ryan,
Wendler Christopher Charles
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb169
Subject(s) - caffeine , in utero , fetus , dna methylation , pregnancy , mesenchymal stem cell , medicine , endocrinology , physiology , biology , gene expression , gene , genetics , pathology
There is growing evidence that alterations in the intrauterine environment can have lasting effects on an individual's health. By disrupting prenatal development, environmental factors can lead to the fetal programming of adult disease, including cardiovascular disease. One substance that fetuses are frequently exposed to is caffeine, which is a non‐selective adenosine receptor antagonist. Caffeine consumption during the first trimester of pregnancy is reported by 60% of pregnant women. Human studies have shown correlations between caffeine use during pregnancy and low birth weight, childhood obesity, and neurodevelopmental deficits in children. Although, all do not accept some of these deleterious effects, it is concerning enough that the United States and many Nordic countries recommend that pregnant women consume less than 200 mg/day, or about 2 cups of coffee a day. Our lab has demonstrated that in utero caffeine exposure in mice produces defects in cardiac gene expression, morphology, and function in adulthood. Furthermore, we have shown that in utero caffeine exposure alters DNA methylation patterns in adult hearts. Based on these data, we hypothesize that in utero caffeine exposure leads to altered DNA methylation that is maintained into adulthood leading to altered gene expression and reduced heart function in adults. It is difficult to study the effects of caffeine on human development at the molecular level. Therefore, we have chosen to examine human mesenchymal stem cells (MSCs) obtained from umbilical cords of infants with known caffeine exposure during development. These cells were obtained from Dr. Kristen Boyle of The Healthy Start Project at the University of Colorado School of Medicine. We obtained a subset of these cell lines that were divided into two groups based on caffeine exposure during pregnancy. Initially, we isolated RNA and DNA from these MSC lines to compare gene expression and DNA methylation between low and high caffeine exposure groups. A global DNA methylation assay revealed that the high caffeine group had a 29.98% decrease in global DNA methylation compared to the low caffeine group (p ≤ 0.01, N = 3). Furthermore, qPCR revealed a 3.5 fold decrease in DNA methyltransferase 3a (DNMT3a) expression in the high caffeine exposure group. DNMT3a is one of three enzymes, including DNMT1 and DNMT3b, responsible for DNA methylation during embryonic development. In summary, our initial results indicate a correlation between high caffeine exposure and reduced global DNA methylation within human MSCs obtained from umbilical cords with known caffeine exposure. In addition, we observed altered gene expression in MSCs exposed to high caffeine levels in utero. Support or Funding Information Children's Miracle Networkat the University of Florida This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .