title: Chronic carbon monoxide inhalation during pregnancy augments uterine artery blood flow and uteroplacental vascular growth in mice.
abstract: End-tidal breath carbon monoxide (CO) is abnormally low in women with preeclampsia (PE), while women smoking during pregnancy have shown an increase in CO levels and a 33% lower incidence of PE. This effect may be, in part, due to lowered sFLT1 plasma levels in smokers, and perhaps low-level CO inhalation can attenuate the development of PE in high-risk women. Our previous work showed maternal chronic CO exposure (<300 ppm) throughout gestation had no maternal or fetal deleterious effects in mice. Our current study evaluated the uteroplacental vascular effects in CD-1 maternal mice that inhaled CO (250 ppm) both chronically, gestation day (GD) 0.5 to 18.5, and acutely, 2.5 h on each of GD 10.5 and 14.5. We demonstrated, using microultrasound measurements of blood velocity and microcomputed tomography imaging of the uteroplacental vasculature, that chronic maternal exposure to CO doubled uterine artery blood flow and augmented uteroplacental vascular diameters and branching. This finding may be of benefit to women with PE, as they exhibit uteroplacental vascular compromise. The ratio of VEGF protein to its FLT1 receptor was increased in the placenta, suggesting a shift to a more angiogenic state; however, maternal circulating levels of VEGF, sFLT1, and their ratio were not significantly changed. Doppler blood velocities in the maternal uterine artery and fetal umbilical artery and vein were unaltered. This study provides in vivo evidence that chronic inhalation of 250 ppm CO throughout gestation augments uterine blood flow and uteroplacental vascular growth, changes that may protect against the subsequent development of preeclampsia.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston General Hospital, Kingston, Ontario, Canada;
authors.forename: Carolina C
authors.initials: CC
authors.lastname: Venditti
authors.forename: Richard
authors.initials: R
authors.lastname: Casselman
authors.forename: Malia S Q
authors.initials: MS
authors.lastname: Murphy
authors.forename: S Lee
authors.initials: SL
authors.lastname: Adamson
authors.forename: John G
authors.initials: JG
authors.lastname: Sled
authors.forename: Graeme N
authors.initials: GN
authors.lastname: Smith
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage*; D005260:Female; D051379:Mice; D010920:Placenta / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism / Q000517:prevention & control; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects*; D055988:Uterine Artery / Q000187:drug effects* / Q000378:metabolism; D014599:Uterus / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D002248:Carbon Monoxide; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: carbon monoxide; placenta; preeclampsia; pregnancy; sFLT1; vascular endothelial growth factor