Vol.:(0123456789) 1 3 Clinical Oral Investigations https://doi.org/10.1007/s00784-023-05155-3 RESEARCH Absence of melatonin during development impairs craniofacial and dental onset in rats Bruno Calsa 1,2  · Ludmilla Scodeler de Camargo 3  · Tainá Jaqueline Bortolança 4  · Camila Andrea de Oliveira 1  · Rosana Catisti 1  · Fernanda Gaspar do Amaral 3,5  · Milton Santamaria‑Jr 1,4,6 Received: 20 October 2022 / Accepted: 11 July 2023 © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023 Abstract Objective Herein, we evaluated pinealectomy-induced melatonin absence to determine its efects on craniofacial and dental development in the ofspring. Design Female Wistar rats in three groups, i.e., intact pregnant rats, pinealectomized pregnant rats (PINX), and pinealec- tomized 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 afect dental and maxil- lary development in ofspring, as well as delay odontogenesis and osteogenesis in maxillary tissues. Clinical relevance Our fndings 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. Keywords Fetal programming · Odontogenesis · Osteogenesis · Melatonin and RANKL/OPG * Milton Santamaria-Jr miltonsantamariajr@gmail.com Bruno Calsa calsabruno@gmail.com 1 Graduate Program of Biomedical Sciences, Hermínio Ometto Foundation - FHO, Araras, SP, Brazil 2 Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Department of Internal Medicine, Faculty of Medical Sciences at State University of Campinas - UNICAMP, Campinas, SP, Brazil 3 Pineal Neurobiology Laboratory, Department of Physiology, Federal University of São Paulo - UNIFESP, São Paulo, SP, Brazil 4 Graduate Program of Orthodontics Hermínio Ometto Foundation - FHO, Araras, SP, Brazil 5 Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo - USP, São Paulo, SP, Brazil 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