In utero nicotine exposure affects murine palate development

Abstract

Objectives: Despite data linking smoking to increased risk of fetal morbidity and mortality, 11% of pregnant women continue to smoke or use alternative nicotine products. Studies confirm that nicotine exposure during pregnancy increases the incidence of birth defects; however, little research has focused on specific anatomic areas based on timing of exposure. We aim to determine critical in utero and postnatal periods of nicotine exposure that affect craniofacial development, specifically palate growth. Malformation of the palatal structures can result in numerous complications including facial growth disturbance, or impeding airway function. We hypothesized that both in utero and postnatal nicotine exposure will alter palate development.

Materials and methods: We administered pregnant C57BL6 mice water supplemented with 100 μg/mL nicotine during early pregnancy, throughout pregnancy, during pregnancy and lactation, or lactation only. Postnatal day 15 pups underwent micro-computed tomography (μCT) analyses specific to the palate.

Results: Resultant pups revealed significant differences in body weight from lactation-only nicotine exposure, and μCT investigation revealed several dimensions affected by lactation-only nicotine exposure, including palate width, palate and cranial base lengths, and mid-palatal suture width.

Conclusions: These results demonstrate the direct effects of nicotine on the developing palate beyond simple tobacco use. Nicotine exposure through tobacco alternatives, cessation methods, and electronic nicotine delivery systems (ENDS) may disrupt normal growth and development of the palate during development and the postnatal periods of breastfeeding. Due to the recent dramatic increase in the use of ENDS, future research will focus specifically on this nicotine delivery method.

Keywords: cephalometric; cranial base; nicotine; palate; suture.

Figure 1.. Effects of maternal nicotine exposure on palatal length of PN15 mice.

Micro-CT analysis (a and b) of three different length measurements (S1, S2, and S3) of the palate in the mid-sagittal plane (b) showed significant decrease in palatal lengths S1 and S2 in the lactation exposure group compared to the early pregnancy exposure (c and d), while the S3 length was significantly decreased in the lactation exposure group compared to controls (e). *p<0.05, **p<0.01. PSES: Pre-Spheno-Ethmoidal Synchondrosis; ISS: Inter-Sphenoidal Synchondrosis; SOS: Spheno-Occipital Synchondrosis.

Figure 2.. Effects of maternal nicotine exposure on mid-palatal suture width of PN15 mice.

Micro-CT analysis (a and b) of the coronal plane (b) showed significant decrease in the mid-palatal suture in the lactation exposure compared to controls (c).*p<0.05

Figure 3.. Effects of maternal nicotine exposure on palatal width of PN15 mice.

Micro-CT analysis (a and b) of three different width measurements (right to left M1, M1/M2, and M2) of the palate in the axial plane (b) showed significant decrease in palatal width at M1 in the lactation only exposure compared to the early pregnancy exposure (c), at the M1/M2 in the lactation only exposure compared to the controls, the early pregnancy exposure, and the pregnancy and lactation exposure (d), and at the M2 in the pregnancy exposure compared to the lactation exposure (e). *p<0.05, **p<0.01, ***p<0.001