Prenatal exposure to environmental tobacco smoke alters gene expression in the developing murine hippocampus.
BACKGROUND
Little is known about the effects of passive smoke exposures on the developing brain.


OBJECTIVE
The purpose of the current study was to identify changes in gene expression in the murine hippocampus as a consequence of in utero exposure to sidestream cigarette smoke (an experimental equivalent of environmental tobacco smoke (ETS)) at exposure levels that do not result in fetal growth inhibition.


METHODS
A whole body smoke inhalation exposure system was utilized to deliver ETS to pregnant C57BL/6J mice for 6 h/day from gestational days 6-17 (gd 6-17) [for microarray] or gd 6-18.5 [for fetal phenotyping].


RESULTS
There were no significant effects of ETS exposure on fetal phenotype. However, 61 "expressed" genes in the gd 18.5 fetal hippocampus were differentially regulated (up- or down-regulated by 1.5-fold or greater) by maternal exposure to ETS. Of these 61 genes, 25 genes were upregulated while 36 genes were down-regulated. A systems biology approach, including computational methodologies, identified cellular response pathways, and biological themes, underlying altered fetal programming of the embryonic hippocampus by in utero cigarette smoke exposure.


CONCLUSIONS
Results from the present study suggest that even in the absence of effects on fetal growth, prenatal smoke exposure can alter gene expression during the "early" period of hippocampal growth and may result in abnormal hippocampal morphology, connectivity, and function.
Mukhopadhyay
Partha
P
University of Louisville Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville, Louisville, Kentucky 40292, USA.
Horn
Kristin H
KH
Greene
Robert M
RM
Michele Pisano
M
M
D000014:Abnormalities, Drug-Induced / Q000235:genetics; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D053263:Gene Regulatory Networks; D005865:Gestational Age; D006624:Hippocampus / Q000002:abnormalities / Q000187:drug effects*; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D014028:Tobacco Smoke Pollution