Embryonic caffeine exposure induces adverse effects in adulthood.
The purpose of this study was to determine both the short-term effects on cardiac development and embryo growth and the long-term effects on cardiac function and body composition of in utero caffeine exposure. Pregnant mice (C57BL/6) were exposed to hypoxia (10% O(2)) or room air from embryonic days (E) 8.5-10.5, and treated with caffeine (20 mg/kg, i.p.) or vehicle (normal saline, 0.9% NaCl). This caffeine dose results in a circulating level that is equivalent to 2 cups of coffee in humans. Hypoxic exposure acutely reduced embryonic growth by 30%. Exposure to a single dose of caffeine inhibited cardiac ventricular development by 53% in hypoxia and 37% in room air. Caffeine exposure resulted in inhibition of hypoxia-induced HIF1alpha protein expression in embryos by 40%. When offspring from dams treated with a single dose of caffeine were studied in adulthood, we observed that caffeine treatment alone resulted in a decrease in cardiac function of 38%, as assessed by echocardiography. We also observed a 20% increase in body fat with male mice exposed to caffeine. Caffeine was dissolved in normal saline, so it was used as a control. Room air controls were used to compare to the hypoxic mice. Exposure to a single dose of caffeine during embryogenesis results in both short-term effects on cardiac development and long-term effects on cardiac function.
Wendler
Christopher C
CC
Yale Child Health Research Center, Department of Pediatrics, Division of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. christopher.wendler@yale.edu
Busovsky-McNeal
Melissa
M
Ghatpande
Satish
S
Kalinowski
April
A
Russell
Kerry S
KS
Rivkees
Scott A
SA
D000818:Animals; D002110:Caffeine / Q000378:metabolism / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D006128:Growth / Q000187:drug effects*; D000860:Hypoxia / Q000378:metabolism; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D013995:Time
D002110:Caffeine