Document Detail

Maternal hypoxia and caffeine exposure depress fetal cardiovascular function during primary organogenesis.
MedLine Citation:
PMID:  22612345     Owner:  NLM     Status:  MEDLINE    
AIMS: Hypoxia is known to influence cardiovascular (CV) function, in part, through adenosine receptor activation. We have shown in a mouse model that during primary cardiac morphogenesis, acute maternal hypoxia negatively affects fetal heart rate, and recurrent maternal caffeine exposure reduces fetal cardiac output (CO) and downregulates fetal adenosine A(2A) receptor gene expression. In the present study, we investigated whether maternal caffeine dosing exacerbates the fetal CV response to acute maternal hypoxia during the primary morphogenesis period.
MATERIAL AND METHODS: Gestational-day-11.5 pregnant mice were exposed to hypoxia (45 s duration followed by 10 min of recovery and repeated 3 times) while simultaneously monitoring maternal and fetal CO using high-resolution echocardiography.
RESULTS:   Following maternal hypoxia exposure, maternal CO transiently decreased and then returned to pre-hypoxia baseline values. In contrast to a uniform maternal cardiac response to each exposure to hypoxia, the fetal CO recovery time to the baseline decreased, and CO rebounded above baseline following the second and third episodes of maternal hypoxia. Maternal caffeine treatment inhibited the fetal CO recovery to maternal hypoxia by lengthening the time to CO recovery and eliminating the CO rebound post-recovery. Selective treatment with an adenosine A(2A) receptor antagonist, but not an adenosine A(1) receptor antagonist, reproduced the altered fetal CO response to maternal hypoxia created by caffeine exposure.
CONCLUSIONS:   Results suggest an additive negative effect of maternal caffeine on the fetal CV response to acute maternal hypoxia, potentially mediated via adenosine A(2A) receptor inhibition during primary cardiovascular morphogenesis.
Nobuo Momoi; Joseph P Tinney; Bradley B Keller; Kimimasa Tobita
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-21
Journal Detail:
Title:  The journal of obstetrics and gynaecology research     Volume:  38     ISSN:  1447-0756     ISO Abbreviation:  J. Obstet. Gynaecol. Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-28     Completed Date:  2014-04-23     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  9612761     Medline TA:  J Obstet Gynaecol Res     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  1343-51     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.
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MeSH Terms
Caffeine / adverse effects*
Fetal Heart / drug effects*
Heart Rate, Fetal / drug effects
Hemodynamics / drug effects
Pregnancy Complications*
Purinergic P1 Receptor Antagonists / adverse effects*
Stroke Volume / drug effects
Grant Support
R01 HL065219/HL/NHLBI NIH HHS; R01 HL065219-05/HL/NHLBI NIH HHS; RFA-R01 H065129//PHS HHS
Reg. No./Substance:
0/Purinergic P1 Receptor Antagonists; 3G6A5W338E/Caffeine

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