Nicotine is known to affect cell proliferation and differentiation, two processes vital to proper development of the mandible. The mandible, the lower jaw in mammals and fish, plays a crucial role in craniofacial development. Malformation of the jaw can precipitate a plethora of complications including disrupting development of the upper jaw, the palate, and or impeding airway function. The purpose of this study was to test the hypothesis that in utero nicotine exposure alters the development of the murine mandible in a dose dependent manner. To test this hypothesis, wild type C57BL6 mice were used to produce in utero nicotine exposed litters by adding nicotine to the drinking water of pregnant dams at concentrations of 0 μg/ml (control), 50 μg/ml (low), 100 μg/ml (medium), 200 μg/ml (high) throughout pregnancy to birth of litters mimicking clinically relevant nicotine exposures. Resultant pups revealed no significant differences in body weight however, cephalometric investigation revealed several dimensions affected by nicotine exposure including mandibular ramus height, mandibular body height, and molar length. Histological investigation of molars revealed an increase in proliferation and a decrease in apoptosis with nicotine exposure. These results demonstrate the direct effects of nicotine on the developing mandible outside the context of tobacco use, indicating that nicotine use including tobacco alternatives, cessation methods, and electronic nicotine delivering products may disrupt normal growth and development of the craniofacial complex.
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Objective Develop a model for the study of Electronic Nicotine Device (ENDS) exposure on craniofacial development. Design Experimental preclinical design followed as pregnant murine dams were randomized and exposed to filtered air exposure, carrier exposure consisting of 50% volume of propylene glycol and vegetable glycine (ENDS Carrier) respectively, or carrier exposure with 20 mg/ml of nicotine added to the liquid vaporizer (ENDS carrier with nicotine). Setting Preclinical murine model exposure using the SciReq exposure system. Participants C57BL6 adult 8 week old female pregnant mice and exposed in utero litters. Interventions Exposure to control filtered air, ENDS carrier or ENDS carrier with nicotine added throughout gestation at 1 puff/minute, 4 h/day, five days a week. Main Outcome Measures Cephalometric measures of post-natal day 15 pups born as exposed litters. Results Data suggests alterations to several facial morphology parameters in the developing offspring, suggesting electronic nicotine device systems may alter facial growth if used during pregnancy. Conclusions Future research should concentrate on varied formulations and exposure regimens of ENDS to determine timing windows of exposures and ENDS formulations that may be harmful to craniofacial development.
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