Embryonic caffeine exposure induces adverse effects in adulthood

Wendler, Christopher C.; Busovsky-McNeal, Melissa; Ghatpande, Satish; Kalinowski, April; Russell, Kerry S.; Rivkees, Scott A.

doi:10.1096/fj.08-124941

Cited by 37 publications

(61 citation statements)

References 31 publications

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“…Considering the above, we tested if caffeine exerts effects on the embryo similar to that seen when A1ARs are deleted 17 . Pregnant mice in room air or hypoxia were treated with a single dose of caffeine at E8.5 resulting in circulating concentrations in the dam equivalent to those seen with two cups of coffee 50 .…”

Section: Effects Of Caffeine On the Embryomentioning

confidence: 99%

Long-term consequences of disrupting adenosine signaling during embryonic development

Rivkees

Wendler

2017

Molecular Aspects of Medicine

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There is growing evidence that disruption in the prenatal environment can have long-lasting effects on an individual’s health in adulthood. Research on the fetal programming of adult diseases, including cardiovascular disease, focuses on epi-mutations, which alter the normal pattern of epigenetic factors such as DNA methylation, miRNA expression, or chromatin modification, rather than traditional genetic alteration. Thus, understanding how in utero chemical exposures alter epigenetics and lead to adult disease is of considerable public health concern. Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists including the methlyxanthines caffeine and theophylline are widely consumed during pregnancy. The receptors that transduce adenosine action are the A1, A2a, A2b, and A3 adenosine receptors (ARs). We examined the long-term effects of in utero disruption of adenosine signaling on cardiac gene expression, morphology, and function in adult offspring. One substance that fetuses are frequently exposed to is caffeine, which is a non-selective adenosine receptor antagonist. Over the past several years, we examined the role of adenosine signaling during embryogenesis and cardiac development. We discovered that in utero alteration in adenosine action leads to adverse effects on embryonic and adult murine hearts. We find that cardiac A1ARs protect the embryo from in utero hypoxic stress, a condition that causes an increase in adenosine levels. After birth in mice, we observed that in utero caffeine exposure leads to abnormal cardiac function and morphology in adults, including an impaired response to β-adrenergic stimulation. Recently, we observed that in utero caffeine exposure induces transgenerational effects on cardiac morphology, function, and gene expression. Our findings indicate that the effects of altered adenosine signaling are dependent on signaling through the A1ARs and timing of disruption. In addition, the long-term effects of altered adenosine signaling appear to be mediated by alterations in DNA methylation, an epigenetic process critical for normal development.

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Section: Effects Of Caffeine On the Embryomentioning

confidence: 99%

Long-term consequences of disrupting adenosine signaling during embryonic development

Rivkees

Wendler

2017

Molecular Aspects of Medicine

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“…These observations give rise to the concept that the intake of caffeine during gestation represents a sort of fetal programming 10 .…”

Section: Introductionmentioning

confidence: 96%

The testis of the mice C57/BL6 offspring in adulthood have alterations due to maternal caffeine consumption

et al. 2014

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PURPOSE:To investigate the effects of the maternal caffeine consumption during pregnancy to adult male testis mice offspring. METHODS:Twenty pregnant mice were divided into control group (c) and caffeine group (cf). dams received daily saline or 20 mg/kg of caffeine subcutaneously. Male offspring were monitored daily until 13 th week. The testis were used to evaluate both the proliferation (pcna) and apoptosis (bax); leptin receptor (ob-r); aromatase; follicle stimulating hormone (fshr), luteinizing hormone (lhr) and androgen receptors (ar); steroidogenic acute regulatory protein (star); vascular endothelial growth factor (vegf) and estrogen receptors (erα and erβ) by western blotting. Serum concentrations of testosterone, estradiol and leptin were measured. RESULTS:There was a significant reduction in food intake and the body mass gain (p<0.05) in the cf ; pcna (p=0.01), fshr (p=0.02), star (p=0.0007), vegf (p=0.009), ar (p=0.03) in the cf. while an increase were note in bax (p=0.01), ob-r (p=0.02), lhr (p=0.04) and in the aromatase (p=0.03) in the cf. only erα and erβ were not changed by maternal caffeine. The serum testosterone levels in the cf offspring were 90% lower than in the c offspring (p=0.04). CONCLUSION:Maternal caffeine consumption has a role and alters the testis of the offspring in adulthood.

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“…Studies examining the association between maternal substance consumption and early infant development have mostly suggested the potential short and long term teratogenic and neurodevelopmental consequences of nicotine [27,28], caffeine [29][30][31], and alcohol use during pregnancy [32], mostly when in the presence of high doses and chronic exposure. Reported development effects include a significant fetal growth reduction [33][34][35][36][37], low birth weight and preterm delivery [26,38,39], more time spent in a low fetal heart rate variation pattern and decrement of fetal activity both in high and low fetal heart rate variation periods [40], delayed onset of response to the maternal voice in fetuses less than 37 weeks gestational age [41] and fetal death [42].…”

Section: Introductionmentioning

confidence: 99%

Mother's anxiety and depression and associated risk factors during early pregnancy: effects on fetal growth and activity at 20–22 weeks of gestation

Conde

Figueiredo

Tendais

et al. 2010

Journal of Psychosomatic Obstetrics & Gynecology

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To examine effects of mother's anxiety and depression and associated risk factors during early pregnancy on fetal growth and activity. Repeated measures of mother's anxiety (State-Anxiety Inventory (STAI-S)) and depression (Edinburgh Postnatal Depression Scale (EPDS)) and related socio demographics and substance consumption were obtained at the 1st and 2nd pregnancy trimesters, and fetus' (N = 147) biometric data and behavior was recorded during ultrasound examination at 20-22 weeks of gestation. Higher anxiety symptoms were associated to both lower fetal growth and higher fetal activity. While lower education, primiparity, adolescent motherhood, and tobacco consumption predicted lower fetal growth, coffee intake predicted lower fetal activity. Vulnerability of fetal development to mother's psychological symptoms as well as to other sociodemographic and substance consumption risk factors during early and mid pregnancy is suggested.

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Embryonic caffeine exposure induces adverse effects in adulthood

Cited by 37 publications

References 31 publications

Long-term consequences of disrupting adenosine signaling during embryonic development

Long-term consequences of disrupting adenosine signaling during embryonic development

The testis of the mice C57/BL6 offspring in adulthood have alterations due to maternal caffeine consumption

Mother's anxiety and depression and associated risk factors during early pregnancy: effects on fetal growth and activity at 20–22 weeks of gestation

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