Carbon monoxide increases utero-placental angiogenesis without impacting pregnancy specific adaptations in mice.

BACKGROUND: 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. FINDINGS: 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. CONCLUSIONS: 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.

Inhaled carbon monoxide increases vasodilation in the microvascular circulation.

Preeclampsia (PE) is characterized by systemic maternal endothelial dysfunction. Changes in endothelial reactivity have been reported before the onset of clinical signs of PE, and continuing into the post-partum period. Women who smoke during pregnancy have a 33% reduced risk of developing PE. This reduced risk is hypothesized to be, in part, attributed to carbon monoxide (CO), a by-product of cigarette combustion and a known endogenous vasodilator. Determining the vascular effects of CO in healthy women, may inform how CO can improve endothelial function and have promise as a novel therapeutic for PE. As part of a pilot study to determine the vascular effects of CO, the aim of this study was to measure microvascular vasodilation following low-dose CO inhalation. Non-pregnant women inhaled ambient room air or 250 ppm CO for 24 min during microvascular assessment using laser speckle contrast imaging. Changes in vascular flux were measured in the forearm before, during, and following a three-minute arterial occlusion. CO inhalation increased end-tidal breath CO (EtCO) (9.1 ±â€¯1.9 vs. 1.8 ±â€¯0.7 ppm, p < 0.05) and increased microvascular vasodilation, measured as difference of maximum level/resting level ratio (mean difference 0.476, 95% confidence interval (CI) = 0.149-0.802 vs. 0.118, 95% CI = -0.425-0.662, p < 0.05). Women who inhaled CO had a longer time to half recovery of endothelial function following arterial occlusion, compared to controls (hazard ratio 0.29, 95% CI = 0.10-0.91, p = 0.033). Inhalation of CO moderately increased EtCO and resulted in an increased microvascular response, suggesting that CO may have potential as a therapeutic for PE.

Creation of plastinated placentas as a novel teaching resource for medical education in obstetrics and gynaecology.

INTRODUCTION: Knowledge of the gross anatomy of the placenta is fundamental in order to help identify potential complications during pregnancy. The placenta is difficult to study without a three-dimensional appreciation of its structure. The aim of this study was to develop a collection of plastinated placenta specimens and accompanying clinical educational materials to provide learning resources for placental abnormalities and their associated pregnancy outcomes. These plastinates and educational modules were used as teaching resources for both undergraduate and post-graduate medical trainees in Obstetrics and Gynaecology. METHODS: Placentas were plastinated by S10 silicone plastination. Clinical education materials were created that included ultrasound images, photographs and information on the associated pregnancy outcomes. Utility of the plastinates was assessed using questionnaires completed by 70 medical students and 33 attendees at the 8th and 9th Annual International Human Placenta Workshop held at Queen's University, Kingston, ON. Attendees included graduate students, post-doctoral fellows, medical residents, research investigators and clinicians. RESULTS: Data collected demonstrated that 76.7% of medical student (n = 60) and 78.1% of Placenta Workshop attendees (n = 32) preferred plastinates as a supplemental learning resource compared to textbooks and images alone (36.7% and 37.5% respectively). All respondents also expressed the desire to have plastinated placentas available for future learning opportunities. DISCUSSION: Plastinated placentas are a valuable addition as teaching resources for many demographic groups with an interest in placental anatomy and pathology. Medical trainees and residents in Obstetrics and Gynaecology would benefit from the availability of plastinates as educational tools.