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Absence of melatonin during development impairs craniofacial and dental onset in rats

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Abstract

Objective

Herein, we evaluated pinealectomy-induced melatonin absence to determine its effects on craniofacial and dental development in the offspring.

Design

Female Wistar rats in three groups, i.e., intact pregnant rats, pinealectomized pregnant rats (PINX), and pinealectomized pregnant rats subjected to oral melatonin replacement therapy, were crossed 30 days after surgery. The heads of 7-day-old pups were harvested for cephalometric and histological analyses, and maxillae and incisors were collected for mRNA expression analysis.

Results

The PINX pups exhibited a reduction in neurocranial and facial parameters such as a decrease in alveolar bone area, incisor size and proliferation, and an increase in odontoblasts and the dentin layer. Based on incisor mRNA expression analysis, we found that Dmp1 expression was upregulated, whereas Col1a1 expression was downregulated. Maxillary mRNA expression revealed that Rankl expression was upregulated, whereas that of Opn and Osx was downregulated.

Conclusion

Our results demonstrated that the absence of maternal melatonin during early life could affect dental and maxillary development in offspring, as well as delay odontogenesis and osteogenesis in maxillary tissues.

Clinical relevance

Our findings suggest that disruptions or a lack of melatonin during pregnancy may cause changes in craniofacial and dental development, at least in animal experiments; however, in humans, these feedings are still poorly understood, and thus careful evaluations of melatonin levels in humans need to be investigated in craniofacial alterations.

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Data availability

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Acknowledgements

The authors thank Sra. Mirelle Oliveira for radiographic image assistance; Me. Lucas Eduardo Orzari and Sra. Renata Barbieri provided technical assistance.

Funding

This work was supported by grants from the Hermínio Ometto Foundation-FHO and the São Paulo Research Foundation (FAPESP - 16/23237-4). T.J. Bortolança was the recipient of an undergraduate fellowship from Programa Iniciação Científica do Conselho Nacional de Pesquisa (PIBIC/CNPq - 143262/2021-1).

Author information

Authors and Affiliations

  1. Graduate Program of Biomedical Sciences, Hermínio Ometto Foundation - FHO, Araras, SP, Brazil

    Bruno Calsa, Camila Andrea de Oliveira, Rosana Catisti & Milton Santamaria-Jr

  2. Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Department of Internal Medicine, Faculty of Medical Sciences at State University of Campinas - UNICAMP, Campinas, SP, Brazil

    Bruno Calsa

  3. Pineal Neurobiology Laboratory, Department of Physiology, Federal University of São Paulo - UNIFESP, São Paulo, SP, Brazil

    Ludmilla Scodeler de Camargo & Fernanda Gaspar do Amaral

  4. Graduate Program of Orthodontics Hermínio Ometto Foundation - FHO, Araras, SP, Brazil

    Tainá Jaqueline Bortolança & Milton Santamaria-Jr

  5. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo - USP, São Paulo, SP, Brazil

    Fernanda Gaspar do Amaral

  6. Department of Social and Pediatric Dentistry, Institute of Science and Technology - College of Dentistry, UNESP - São Paulo State University, Av. Eng. Francisco José Longo 777, São José Dos Campos, SP, 12245-000, Brazil

    Milton Santamaria-Jr

Authors
  1. Bruno Calsa
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  2. Ludmilla Scodeler de Camargo
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  4. Camila Andrea de Oliveira
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  5. Rosana Catisti
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  7. Milton Santamaria-Jr
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Contributions

Conceptualization: B Calsa, LS de Camargo, FG do Amaral, M Santamaria-Jr; Data curation: B Calsa; Formal analysis: B Calsa, LS de Camargo, CA de Oliveira, R Catisti, FG do Amaral, M Santamaria-Jr; Funding acquisition: M Santamaria-Jr; Investigation: B Calsa, LS de Camargo, TJ Bortolança, CA de Oliveira; Methodology: B Calsa, LS de Camargo, R Catisti, FG do Amaral, M Santamaria-Jr; Project administration: FG do Amaral, M Santamaria-Jr; Supervision: R Catisti, FG do Amaral, M Santamaria-Jr; Writing - original draft: B Calsa, LS de Camargo, TJ Bortolança; Writing - review & editing: B Calsa, CA de Oliveira, R Catisti, FG do Amaral, M Santamaria-Jr.

Corresponding author

Correspondence to Milton Santamaria-Jr.

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Ethical approval

All the protocols followed by this research were previously approved by the Ethical Committee in Animal Experimentation from the Federal University of São Paulo, Brazil (#8074220415).

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Calsa, B., de Camargo, L.S., Bortolança, T.J. et al. Absence of melatonin during development impairs craniofacial and dental onset in rats. Clin Oral Invest 27, 5353–5365 (2023). https://doi.org/10.1007/s00784-023-05155-3

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