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

Odontology volume 111, pages 401–408 (2023)Cite this article

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.

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Data availability

Raw data are available as supplementary material (Tables S1 and S2).

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Acknowledgements

The authors are grateful to the Histology Technicians of the Department of General Biology of the State University of Londrina, Mr. Carlos Lourenço and Ms. Melyssa Costa.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors and was funded by the researchers’ own resources.

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Authors and Affiliations

  1. Department of General Biology, State University of Londrina, Km 380, Celso Garcia Cid Road., Londrina, 86057-970, Brazil

    Márjori Frítola, Camila Salvador Sestario, Caio Cezar Nantes Martins, Bruna Santos Ezequiel & Maria José Sparça Salles

  2. School of Biological Sciences, University of Aberdeen, Zoology Building, Tillydrone Ave, Aberdeen, AB24 2TZ, UK

    Juliano Morimoto

Authors
  1. Márjori Frítola
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  4. Bruna Santos Ezequiel
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  6. Maria José Sparça Salles
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Contributions

Márjori Frítola: conceptualization (supporting); data curation (lead); formal analysis (supporting); investigation (lead); methodology (equal); project administration (lead); validation (equal); visualization (equal); writing—original draft (lead); writing—review and editing (equal).

Camila Salvador Sestario: investigation (supporting); methodology (equal); project administration (supporting); validation (equal); writing—review and editing (equal).

Caio Cezar Nantes Martins: investigation (supporting); methodology (equal); project administration (supporting); validation (equal); writing—review and editing (supporting).

Bruna Santos Ezequiel: investigation (supporting); methodology (equal); project administration (supporting); validation (supporting); writing—review and editing (supporting).

Juliano Morimoto: data curation (supporting); formal analysis (lead); supervision (supporting); validation (equal); visualization (equal); writing—original draft (supporting); writing—review and editing (equal).

Maria José Sparça Salles: conceptualization (lead); funding acquisition (lead); project administration (supporting); resources (lead); supervision (lead); validation (equal); visualization (equal); writing—original draft (supporting); writing—review and editing (equal).

All authors gave their final approval and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Maria José Sparça Salles.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical statement

All procedures described in this study abide with ARRIVE guidelines and are in accordance with the Brazilian Directive for the Care and Use of Animals for Scientific Purposes and Teaching and with the European Communities Council Directive of 24 November 1986 (86/609/EEC). Ethical approval was obtained via the Ethics Committee for Animal Experimentation of the State University of Londrina (process number: 15688.2017.30, official letter 112/2017). All the authors mentioned in the manuscript have agreed for authorship, read, and approved the final version of the manuscript, and given consent for submission and subsequent publication of the manuscript.

Statement of animal welfare

The mice from the sample were kept under controlled conditions to guarantee their welfare: 12 h light/dark cycles, temperature set at 22 ± 2 °C and unlimited access to water and food. Besides, the animals were allocated in a proportion of two females for each male mice, in 30 cm × 20 cm × 13 cm polypropylene cages lined with wood shavings. Only two people conducted the treatments and euthanasia out of the research team, as quickly and as comfortably as possible.

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Frítola, M., Sestario, C.S., Martins, C.C.N. et al. Intrauterine exposure to omeprazole increases the risk of teeth morphological anomalies in the offspring of a murine model. Odontology 111, 401–408 (2023). https://doi.org/10.1007/s10266-022-00749-x

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