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Embryonic caffeine acts via A1 adenosine receptors to induce adverse effects in adulthood
Author(s) -
Wendler Christopher Charles,
Buscariollo Daniela,
Fang Xiefan,
Greenwood Victoria,
Rivkees Scott
Publication year - 2012
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.26.1_supplement.83.4
Subject(s) - caffeine , adenosine , endocrinology , medicine , adenosine receptor , adenosine a1 receptor , offspring , in utero , ventricle , theophylline , adenosine a2a receptor , receptor , adenosine receptor antagonist , biology , chemistry , fetus , pregnancy , genetics , agonist
Previous research demonstrated that caffeine exposure during pregnancy had long‐term effects into adulthood, including altered cardiac function and increased body fat. Caffeine is a non‐selective adenosine receptor antagonist and adenosine A1 receptor (A1AR) is the predominant adenosine receptor expressed during early embryogenesis. The purpose of our current study is to determine whether A1ARs mediate the long‐term effects of caffeine. A1AR knockout mice were mated and injected at E8.5 with 20 mg/kg of caffeine or vehicle. Dams gave birth and offspring were examined at 8–10 weeks of age. Male A1AR+/+ mice treated with caffeine were heavier than controls but there was no difference in percent body fat. Using echocardiography, we revealed that A1AR+/+ caffeine mice had altered cardiac function and morphology as adults. Caffeine caused an increase in % fractional shortening, while also leading to increased thickening of the left ventricle wall concurrent with decreased left ventricle inner diameter. Next, we examined methylation patterns of DNA isolated from adult left ventricles. Methylation arrays from Nimblegen revealed that caffeine increased methylation of DNA in A1AR+/+ hearts compared to A1AR+/+ controls. Since all parameters examined were only altered when A1AR was expressed and not when A1AR had been deleted, we conclude that long‐term effects of in utero caffeine exposure are mediated by A1ARs.