Carbon monoxide increases utero-placental angiogenesis without impacting pregnancy specific adaptations in mice
Open Access
- 14 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Reproductive Biology and Endocrinology
- Vol. 18 (1), 1-7
- https://doi.org/10.1186/s12958-020-00594-z
Abstract
Cigarette smokers have a reduced risk of developing preeclampsia, possibly attributed to an increase in carbon monoxide (CO) levels. Carbon monoxide is a gasotransmitter that has been implicated in maintaining vascular tone, increasing angiogenesis, and reducing inflammation and apoptosis at physiological concentrations. Moderately increasing CO concentrations may have therapeutic potential to prevent or treat preeclampsia; however, the effects of CO on pregnancy are under studied. Our objective was to investigate the effect of CO on major angiogenic and inflammatory markers in pregnancy, and to evaluate the effect of CO on indicators of placental health. Pregnant CD-1 mice were constantly exposed to either ambient air or 250 ppm CO from conception until gestation day (GD)10.5 or GD16.5. Using a qRT-PCR array, we identified that CO increased expression of major angiogenic genes at the implantation site on GD10.5, but not GD16.5. Pro-inflammatory cytokines in the plasma and tissue lysates from implantation sites in treated mice were not significantly different compared to controls. Additionally, CO did not alter the implantation site phenotype, in terms of proliferative capacity, invasiveness of trophoblasts, or abundance of uterine natural killer cells. This study suggests that CO exposure is pro-angiogenic at the maternal-fetal interface, and is not associated with demonstrable concerns during murine pregnancy. Future studies are required to validate safety and efficacy of CO as a potential therapeutic for vascular insufficiency diseases such as preeclampsia and intrauterine growth restriction.Keywords
Funding Information
- Ontario Graduate Scholarship
- Canadian Institutes of Health Research
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