Frítola Márjori, Sestario Camila Salvador, Martins Caio Cezar Nantes, Ezequiel Bruna Santos, Morimoto Juliano, Salles Maria José Sparça
Department of General Biology, State University of Londrina, Km 380, Celso Garcia Cid Road., Londrina, 86057-970, Brazil.
School of Biological Sciences, University of Aberdeen, Zoology Building, Tillydrone Ave, Aberdeen, AB24 2TZ, UK.
Odontology. 2023 Apr;111(2):401-408. doi: 10.1007/s10266-022-00749-x. Epub 2022 Oct 1.
Conditions experienced in early life have long-lasting effects on offspring health. Despite this, little is known about how maternal exposure to drugs during pregnancy affects offspring teeth morphogenesis. In humans, omeprazole is a common drug used to mitigate Gastroesophageal Reflux Disease. Importantly, omeprazole is a non-specific proton-pump inhibitor, which may inhibit the proton pumps expressed in the developing tooth germ. To date, however, the effects of intrauterine life exposure to omeprazole on offspring tooth development remain unknown. In this study, we addressed this gap in a murine model. Pregnant female Swiss mice were exposed to daily doses of 40 mg/kg of omeprazole from the 5 to the 17 day of pregnancy and the effects of such exposure on offspring odontogenesis parameters such as morphological abnormalities, disruptions in the ameloblast and odontoblast layers and the presence of dentin matrix were measured. Omeprazole exposure significantly increased the prevalence (control: 21.6%; treatment: 60%; p = 0.001) and the risk (posterior mean and 95% credible interval; control: 0.230 [0.129; 0.347]; treatment: 0.593 [0.449; 0.730]) of offspring teeth morphological abnormalities, although there were no statistically significant effects of omeprazole exposure on other parameters of tooth development. These findings suggest that there are potential side-effects to offspring oral health of omeprazole use during pregnancy.
早年经历的状况会对后代健康产生长期影响。尽管如此，关于孕期母亲接触药物如何影响后代牙齿形态发生，人们知之甚少。在人类中，奥美拉唑是一种用于缓解胃食管反流病的常用药物。重要的是，奥美拉唑是一种非特异性质子泵抑制剂，它可能会抑制发育中的牙胚中表达的质子泵。然而，迄今为止，子宫内接触奥美拉唑对后代牙齿发育的影响仍不清楚。在本研究中，我们在小鼠模型中填补了这一空白。怀孕的雌性瑞士小鼠在怀孕第5天至第17天每天接受40mg/kg的奥美拉唑剂量，并测量这种接触对后代牙发生参数的影响，如形态异常、成釉细胞层和牙本质细胞层的破坏以及牙本质基质的存在。奥美拉唑暴露显著增加了后代牙齿形态异常的发生率（对照组：21.6%；治疗组：60%；p = 0.001）和风险（后验均值和95%可信区间；对照组：0.230[0.129；0.347]；治疗组：0.593[0.449；0.730]），尽管奥美拉唑暴露对牙齿发育的其他参数没有统计学上的显著影响。这些发现表明，孕期使用奥美拉唑对后代口腔健康存在潜在副作用。
