Mandible development under gestational protein restriction: cellular and molecular mechanisms.

Autor: Calsa B; Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Department of Internal Medicine, FCM, Campinas State University (UNICAMP), Campinas, SP, Brazil., Menezes LDS; Department of Restorative Dentistry, Dental Materials Division, Piracicaba Dental School, UNICAMP, Piracicaba, SP, Brazil., Neves JG; Department of Restorative Dentistry, Dental Materials Division, Piracicaba Dental School, UNICAMP, Piracicaba, SP, Brazil., Gontijo JAR; Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Department of Internal Medicine, FCM, Campinas State University (UNICAMP), Campinas, SP, Brazil., Santamaria-Jr M; Department of Social and Pediatric Dentistry, Institute of Science and Technology, College of Dentistry, São Paulo State University, São Jose dos Campos, Sao Paulo, Brazil., Boer PA; Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Department of Internal Medicine, FCM, Campinas State University (UNICAMP), Campinas, SP, Brazil. boer@unicamp.br.
Jazyk: angličtina
Zdroj: Journal of molecular histology [J Mol Histol] 2024 Oct; Vol. 55 (5), pp. 937-953. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1007/s10735-024-10242-0
Abstrakt: Insufficient evidence regarding how maternal undernutrition affects craniofacial bone development persists. With its unique focus on the impact of gestational protein restriction on calvaria and mandible osteogenesis, this study aims to fill, at least in part, this gap. Female mice were mated and randomized into NP (normal protein) or LP (low protein) groups. On the 18th gestational day (GD), male embryos were collected and submitted to microtomography (µCT), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), PCR, and autophagy dynamic analyses. The study shows that the LP offspring exhibited lower body mass than the NP group, with µCT analysis revealing no volumetric differences in fetus's head. EDS analysis showed lower calcium and higher phosphorus percentages in mandibles and calvaria. SEM assessment evidenced higher hydroxyapatite crystal-like (HC) deposition on the calvaria surface in LP fetus. Conversely, lower HC deposition was observed on the mandible surface, suggesting delayed matrix mineralization in LP fetuses with a higher percentage of collagen fibers in the mandible bone. The autophagy process was reduced in the mesenchyme of LP fetuses. PCR array analysis of 84 genes revealed 27 genes with differential expression in the LP progeny-moreover, increased mRNA levels of Akt1, Mtor, Nfkb, and Smad1 in the LP offspring. In conclusion, the results suggest that gestational protein restriction anticipated bone differentiation in utero, before 18GD, where this process is reduced compared to the control, leading to the reduction in bone area at 15 postnatal day previously observed. These findings provide insights into the molecular and cellular mechanisms of mandible development and suggest potential implications for the Developmental Origins of Health and Disease (DOHaD).
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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