Skip to main content
Top
Published in: Odontology 2/2023

01-10-2022 | Omeprazole | Original Article

Intrauterine exposure to omeprazole increases the risk of teeth morphological anomalies in the offspring of a murine model

Authors: Márjori Frítola, Camila Salvador Sestario, Caio Cezar Nantes Martins, Bruna Santos Ezequiel, Juliano Morimoto, Maria José Sparça Salles

Published in: Odontology | Issue 2/2023

Login to get access

Abstract

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 5th to the 17th 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.
Literature
1.
go back to reference Legoff L, D’Cruz SC, Tevosian S, Primig M, Smagulova F. Transgenerational inheritance of environmentally induced epigenetic alterations during mammalian development. Cells. 2019;8:1–26.CrossRef Legoff L, D’Cruz SC, Tevosian S, Primig M, Smagulova F. Transgenerational inheritance of environmentally induced epigenetic alterations during mammalian development. Cells. 2019;8:1–26.CrossRef
2.
go back to reference Morimoto J, Ponton F, Tychsen I, Cassar J, Wigby S. Interactions between the developmental and adult social environments mediate group dynamics and offspring traits in Drosophila melanogaster. Sci Rep. 2017;7:1–11.CrossRef Morimoto J, Ponton F, Tychsen I, Cassar J, Wigby S. Interactions between the developmental and adult social environments mediate group dynamics and offspring traits in Drosophila melanogaster. Sci Rep. 2017;7:1–11.CrossRef
3.
go back to reference Ravelli G-P, Stein ZA, Susser M. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976;295:349–53.CrossRefPubMed Ravelli G-P, Stein ZA, Susser M. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976;295:349–53.CrossRefPubMed
4.
go back to reference Jacobsen PE, Henriksen TB, Haubek D, Østergaard JR. Developmental enamel defects in children prenatally exposed to anti-epileptic drugs. PLoS ONE. 2013;8:1–6.CrossRef Jacobsen PE, Henriksen TB, Haubek D, Østergaard JR. Developmental enamel defects in children prenatally exposed to anti-epileptic drugs. PLoS ONE. 2013;8:1–6.CrossRef
5.
go back to reference Li CM, Zhernakova A, Engstrand L, Wijmenga C, Brusselaers N. Systematic review with meta-analysis: the risks of proton pump inhibitors during pregnancy. Aliment Pharmacol Ther. 2020;51:410–20.CrossRefPubMed Li CM, Zhernakova A, Engstrand L, Wijmenga C, Brusselaers N. Systematic review with meta-analysis: the risks of proton pump inhibitors during pregnancy. Aliment Pharmacol Ther. 2020;51:410–20.CrossRefPubMed
6.
go back to reference Pascon T, Barbosa AMP, Cordeiro RCL, Bussaneli DG, Prudencio CB, Nunes SK, et al. Prenatal exposure to gestational diabetes mellitus increases developmental defects in the enamel of offspring. PLoS ONE. 2019;14:1–17.CrossRef Pascon T, Barbosa AMP, Cordeiro RCL, Bussaneli DG, Prudencio CB, Nunes SK, et al. Prenatal exposure to gestational diabetes mellitus increases developmental defects in the enamel of offspring. PLoS ONE. 2019;14:1–17.CrossRef
7.
go back to reference Lima KS, Salles AES, de Araújo Costa G, Yokoyama MF, de Paula Ramos S, Paixão-Côrtes VR, et al. Methylphenidate effects on mice odontogenesis and connections with human odontogenesis. Odontology. 2020 Lima KS, Salles AES, de Araújo Costa G, Yokoyama MF, de Paula Ramos S, Paixão-Côrtes VR, et al. Methylphenidate effects on mice odontogenesis and connections with human odontogenesis. Odontology. 2020
8.
go back to reference Lopes-Fatturi A, Menezes JVNB, Fraiz FC, Assunção LR da S, de Souza JF. Systemic exposures associated with hypomineralized primary second molars. Pediatr Dent 2019; 41:364–70. Lopes-Fatturi A, Menezes JVNB, Fraiz FC, Assunção LR da S, de Souza JF. Systemic exposures associated with hypomineralized primary second molars. Pediatr Dent 2019; 41:364–70.
10.
go back to reference Zielinski R, Searing K, Deibel M. Gastrointestinal distress in pregnancy: prevalence, assessment, and treatment of 5 common minor discomforts. J Perinat Neonatal Nurs. 2015;29:23–31.CrossRefPubMed Zielinski R, Searing K, Deibel M. Gastrointestinal distress in pregnancy: prevalence, assessment, and treatment of 5 common minor discomforts. J Perinat Neonatal Nurs. 2015;29:23–31.CrossRefPubMed
11.
go back to reference Fill Malfertheiner S, Malfertheiner MV, Kropf S, Costa SD, Malfertheiner P. A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy. BMC Gastroenterol. 2012;12:1–7.CrossRef Fill Malfertheiner S, Malfertheiner MV, Kropf S, Costa SD, Malfertheiner P. A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy. BMC Gastroenterol. 2012;12:1–7.CrossRef
12.
go back to reference Body C, Christie JA. Gastrointestinal diseases in pregnancy: nausea, vomiting, hyperemesis gravidarum, gastroesophageal reflux disease, constipation, and diarrhea. Gastroenterol Clin NA. 2016;45:267–83.CrossRef Body C, Christie JA. Gastrointestinal diseases in pregnancy: nausea, vomiting, hyperemesis gravidarum, gastroesophageal reflux disease, constipation, and diarrhea. Gastroenterol Clin NA. 2016;45:267–83.CrossRef
13.
go back to reference Sigterman KE, van Pinxteren B, Bonis PA, Lau J, Numans ME. Short-term treatment with proton pump inhibitors, H2- receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease (Review). Cochrane Collab. 2013;1:1–84. Sigterman KE, van Pinxteren B, Bonis PA, Lau J, Numans ME. Short-term treatment with proton pump inhibitors, H2- receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease (Review). Cochrane Collab. 2013;1:1–84.
14.
go back to reference Thélin CS, Richter JE. Review article: the management of heartburn during pregnancy and lactation. Aliment Pharmacol Ther. 2020;2020:421–34.CrossRef Thélin CS, Richter JE. Review article: the management of heartburn during pregnancy and lactation. Aliment Pharmacol Ther. 2020;2020:421–34.CrossRef
15.
go back to reference Savarino V, Dulbecco P, de Bortoli N, Ottonello A, Savarino E. The appropriate use of proton pump inhibitors (PPIs): need for a reappraisal. Eur J Intern Med. 2017;37:19–24.CrossRefPubMed Savarino V, Dulbecco P, de Bortoli N, Ottonello A, Savarino E. The appropriate use of proton pump inhibitors (PPIs): need for a reappraisal. Eur J Intern Med. 2017;37:19–24.CrossRefPubMed
16.
go back to reference Moore J, Flynn RJ, Sampaio M, Wilson CM, Gillon KRW. Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia. Anaesthesia. 1989;44:559–62.CrossRefPubMed Moore J, Flynn RJ, Sampaio M, Wilson CM, Gillon KRW. Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia. Anaesthesia. 1989;44:559–62.CrossRefPubMed
17.
go back to reference He J, Shi XY, Li ZM, Pan XH, Li ZL, Chen Y, et al. Proton pump inhibitors can reverse the YAP mediated paclitaxel resistance in epithelial ovarian cancer. BMC Mol Cell Biol. 2019;20:1–14.CrossRef He J, Shi XY, Li ZM, Pan XH, Li ZL, Chen Y, et al. Proton pump inhibitors can reverse the YAP mediated paclitaxel resistance in epithelial ovarian cancer. BMC Mol Cell Biol. 2019;20:1–14.CrossRef
18.
go back to reference Kanagaratham C, El Ansari YS, Sallis BF, Hollister BMA, Lewis OL, Minnicozzi SC, et al. Omeprazole inhibits IgE-mediated mast cell activation and allergic inflammation induced by ingested allergen in mice. J Allergy Clin Immunol. 2020;146:884–93.CrossRefPubMedPubMedCentral Kanagaratham C, El Ansari YS, Sallis BF, Hollister BMA, Lewis OL, Minnicozzi SC, et al. Omeprazole inhibits IgE-mediated mast cell activation and allergic inflammation induced by ingested allergen in mice. J Allergy Clin Immunol. 2020;146:884–93.CrossRefPubMedPubMedCentral
19.
go back to reference Moriyama Y, Patel V, Ueda I, Futai M. Evidence for a common binding-site for omeprazole and n-ethylmaleimide in subunit a of chromaffin granule vacuolar-type H+-ATPase. Biochem Biophys Res Commun. 1993;1993:699–706.CrossRef Moriyama Y, Patel V, Ueda I, Futai M. Evidence for a common binding-site for omeprazole and n-ethylmaleimide in subunit a of chromaffin granule vacuolar-type H+-ATPase. Biochem Biophys Res Commun. 1993;1993:699–706.CrossRef
20.
go back to reference Johnson L, Ganss B, Wang A, Zirngibl RA, Johnson DE, Owen C, et al. V-ATPases containing a3 subunit play a direct role in enamel development in mice. J Cell Biochem. 2017;118:3328–40.CrossRefPubMed Johnson L, Ganss B, Wang A, Zirngibl RA, Johnson DE, Owen C, et al. V-ATPases containing a3 subunit play a direct role in enamel development in mice. J Cell Biochem. 2017;118:3328–40.CrossRefPubMed
21.
go back to reference Josephsen K, Takano Y, Frische S, Praetorius J, Nielsen S, Aoba T, et al. Ion transporters in secretory and cyclically modulating ameloblasts : a new hypothesis for cellular control of preeruptive enamel maturation. Am J Physiol Physiol. 2010;299:C1299–307.CrossRef Josephsen K, Takano Y, Frische S, Praetorius J, Nielsen S, Aoba T, et al. Ion transporters in secretory and cyclically modulating ameloblasts : a new hypothesis for cellular control of preeruptive enamel maturation. Am J Physiol Physiol. 2010;299:C1299–307.CrossRef
22.
go back to reference Sarkar J, Wen X, Simanian EJ, Paine ML. V-type ATPase proton pump expression during enamel formation. Matrix Biol International Society of Matrix Biology. 2016;52–54:234–45.CrossRef Sarkar J, Wen X, Simanian EJ, Paine ML. V-type ATPase proton pump expression during enamel formation. Matrix Biol International Society of Matrix Biology. 2016;52–54:234–45.CrossRef
23.
go back to reference Sasaki T, Tadokoro K, Yanagisawa T, Higashi S, Garant PR. H+-K+-ATPase activity in the rat incisor enamel organ during enamel formation. Anat Rec. 1988;221:823–33.CrossRefPubMed Sasaki T, Tadokoro K, Yanagisawa T, Higashi S, Garant PR. H+-K+-ATPase activity in the rat incisor enamel organ during enamel formation. Anat Rec. 1988;221:823–33.CrossRefPubMed
25.
go back to reference Calderon IMP, Rudge MVC, Brasil MAM, Henry MACA. Diabete e gravidez experimental em ratas: I. Induçäo do diabete, obtençäo e evoluçäo da prenhez. Acta Cirúrgica Bras. 1992;7:142–6. Calderon IMP, Rudge MVC, Brasil MAM, Henry MACA. Diabete e gravidez experimental em ratas: I. Induçäo do diabete, obtençäo e evoluçäo da prenhez. Acta Cirúrgica Bras. 1992;7:142–6.
26.
go back to reference Cerri PS, de Faria FP, Gazoni Villa R, Katchburian E. Light microscopy and computer three-dimensional reconstruction of the blood capillaries of the enamel organ of rat molar tooth germs. J Anat. 2004;204:191–5.CrossRefPubMedPubMedCentral Cerri PS, de Faria FP, Gazoni Villa R, Katchburian E. Light microscopy and computer three-dimensional reconstruction of the blood capillaries of the enamel organ of rat molar tooth germs. J Anat. 2004;204:191–5.CrossRefPubMedPubMedCentral
27.
go back to reference Yang J, Zhu L, Yuan G, Chen Y, Zhang L, Zhang L, et al. Autophagy appears during the development of the mouse lower first molar. Histochem Cell Biol. 2013;139:109–18.CrossRefPubMed Yang J, Zhu L, Yuan G, Chen Y, Zhang L, Zhang L, et al. Autophagy appears during the development of the mouse lower first molar. Histochem Cell Biol. 2013;139:109–18.CrossRefPubMed
28.
go back to reference R Core Team. R: A language and environment for statistical computing. Vienna: R Found Stat Comput; 2019. R Core Team. R: A language and environment for statistical computing. Vienna: R Found Stat Comput; 2019.
29.
go back to reference Wickham H. ggplot2: elegant graphics for data analysis. Berlin: Springer; 2016.CrossRef Wickham H. ggplot2: elegant graphics for data analysis. Berlin: Springer; 2016.CrossRef
30.
go back to reference Bates D, Sarkar D, Bates MD, Matrix L. The lme4 package. R Packag version. 2007;2:74. Bates D, Sarkar D, Bates MD, Matrix L. The lme4 package. R Packag version. 2007;2:74.
31.
go back to reference Fox J, Weisberg S, Adler D, Bates D, Baud-Bovy G, Ellison S, et al. Package ‘car.’ Vienna R Found Stat Comput. 2012 Fox J, Weisberg S, Adler D, Bates D, Baud-Bovy G, Ellison S, et al. Package ‘car.’ Vienna R Found Stat Comput. 2012
32.
go back to reference Brook A, Jernvall J, Smith R, Hughes T, Townsend G. The dentition : the outcomes of morphogenesis leading to variations of tooth number, size and shape. Aust Dent J. 2014;59:1–12.CrossRefPubMed Brook A, Jernvall J, Smith R, Hughes T, Townsend G. The dentition : the outcomes of morphogenesis leading to variations of tooth number, size and shape. Aust Dent J. 2014;59:1–12.CrossRefPubMed
33.
go back to reference Nikfar S, Abdollahi M, Moretti ME, Magee LA, Koren G. Use of proton pump inhibitors during pregnancy and breastfeeding. Dig Dis Sci. 2002;47:1526–9.CrossRefPubMed Nikfar S, Abdollahi M, Moretti ME, Magee LA, Koren G. Use of proton pump inhibitors during pregnancy and breastfeeding. Dig Dis Sci. 2002;47:1526–9.CrossRefPubMed
34.
go back to reference Gill SK, O’Brien L, Einarson TR, Koren G. The safety of proton pump inhibitors (PPIs) in pregnancy: A meta-analysis. Am J Gastroenterol. 2009;104:1541–5.CrossRefPubMed Gill SK, O’Brien L, Einarson TR, Koren G. The safety of proton pump inhibitors (PPIs) in pregnancy: A meta-analysis. Am J Gastroenterol. 2009;104:1541–5.CrossRefPubMed
35.
go back to reference Källén BAJ. Use of omeprazole during pregnancy - No hazard demonstrated in 955 infants exposed during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2001;96:63–8.CrossRefPubMed Källén BAJ. Use of omeprazole during pregnancy - No hazard demonstrated in 955 infants exposed during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2001;96:63–8.CrossRefPubMed
36.
go back to reference Lalkin A, Loebstein R, Addis A, Ramezani-Namin F, Mastroiacovo P, Mazzone T, et al. The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol. 1998;179:727–30.CrossRefPubMed Lalkin A, Loebstein R, Addis A, Ramezani-Namin F, Mastroiacovo P, Mazzone T, et al. The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol. 1998;179:727–30.CrossRefPubMed
37.
go back to reference Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. Obstet Gynecol Surv. 2011;66:195–7.CrossRef Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. Obstet Gynecol Surv. 2011;66:195–7.CrossRef
38.
go back to reference Bronckers ALJJ, Lyaruu DM, Denbesten PK. Critical review in oral biology and medicine: the impact of fluoride on ameloblasts and the mechanisms of enamel fluorosis. J Dent Res. 2009;88:877–93.CrossRefPubMedPubMedCentral Bronckers ALJJ, Lyaruu DM, Denbesten PK. Critical review in oral biology and medicine: the impact of fluoride on ameloblasts and the mechanisms of enamel fluorosis. J Dent Res. 2009;88:877–93.CrossRefPubMedPubMedCentral
39.
go back to reference Kalinderi K, Delkos D, Kalinderis M, Athanasiadis A, Kalogiannidis I. Urinary tract infection during pregnancy: current concepts on a common multifaceted problem. J Obstet Gynaecol (Lahore). 2018;38:448–53.CrossRef Kalinderi K, Delkos D, Kalinderis M, Athanasiadis A, Kalogiannidis I. Urinary tract infection during pregnancy: current concepts on a common multifaceted problem. J Obstet Gynaecol (Lahore). 2018;38:448–53.CrossRef
40.
go back to reference Mihalaş E, Matricala L, Chelmuş A, Gheţu N, Petcu A, Paşca S. The role of chronic exposure to amoxicillin/clavulanic acid on the developmental enamel defects in mice. Toxicol Pathol. 2016;44:61–70.CrossRefPubMed Mihalaş E, Matricala L, Chelmuş A, Gheţu N, Petcu A, Paşca S. The role of chronic exposure to amoxicillin/clavulanic acid on the developmental enamel defects in mice. Toxicol Pathol. 2016;44:61–70.CrossRefPubMed
Metadata
Title
Intrauterine exposure to omeprazole increases the risk of teeth morphological anomalies in the offspring of a murine model
Authors
Márjori Frítola
Camila Salvador Sestario
Caio Cezar Nantes Martins
Bruna Santos Ezequiel
Juliano Morimoto
Maria José Sparça Salles
Publication date
01-10-2022
Publisher
Springer Nature Singapore
Published in
Odontology / Issue 2/2023
Print ISSN: 1618-1247
Electronic ISSN: 1618-1255
DOI
https://doi.org/10.1007/s10266-022-00749-x

Other articles of this Issue 2/2023

Odontology 2/2023 Go to the issue