Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment

Abstract

With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO2 aerosols (171 ± 6 nm, 10.1 ± 0.39 mg/m3, 5 h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 ± 1.65 μg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10−4 M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated.

Thrombospondin-1 mediates multi-walled carbon nanotube induced impairment of arteriolar dilation

“…For example, activated leukocytes released from the lung adhering to and rolling on the venular walls is known to increase ROS activity (Stapleton et al, 2007). Our observation that leukocyte adhesion and rolling was enhanced in WT mice after pulmonary MWCNT exposure is in agreement with previous work with pulmonary exposure to other particulate matter (Nurkiewicz et al, 2004; Stapleton et al, 2015). Our data represent the first demonstration that the loss of TSP-1 afforded protection to the microvasculature, as evidenced by reduced leukocyte rolling in TSP-1 KO compared to WT MWCNT exposed mice.…”

Metal Nanomaterial Toxicity Variations Within the Vascular System

“…In isolated subepicardial arterioles of rats exposed to TiO 2 -NP, (primary particle diameter −21 nm) a significant impairment in endothelium-dependent vasodilation was noted (94). Similar findings were reported in other vascular beds including the uterus (95), and in skeletal muscle (96). This endothelium-dependent microvascular dysfunction has been linked with a reduced NO bioavailability triggered by the generation of reactive oxygen species following exposure or via the initiation of inflammatory mechanisms in the lung, resulting in the systemic release of cytokines, or within the vascular wall itself (97;98).…”

Inhalation exposure to three-dimensional printer emissions stimulates acute hypertension and microvascular dysfunction

“…We have previously observed this type of dysfunction after pulmonary exposure to nanomaterials such as titanium dioxide (Nurkiewicz et al , 2011; Stapleton et al , 2015), cerium dioxide (Minarchick et al , 2013; Minarchick et al , 2015), and carbon nanotubes (Stapleton et al , 2012). However, single toxicant based studies do not accurately relate to the complexity of emissions generated by the 3D printing process.…”