Mandible development under gestational protein restriction: cellular and molecular mechanisms

Area of Science:

• Developmental Biology
• Craniofacial Development
• Nutritional Science

Background:

• Maternal undernutrition's effects on craniofacial bone development are not well understood.
• Gestational protein restriction is a significant nutritional challenge with potential developmental consequences.

Purpose of the Study:

• To investigate the impact of gestational protein restriction on calvaria and mandible osteogenesis in mouse embryos.
• To elucidate the molecular and cellular mechanisms underlying altered craniofacial bone development due to maternal protein deficiency.

Main Methods:

• Mice were fed normal protein (NP) or low protein (LP) diets during gestation.
• Embryos at gestational day 18 (GD18) were analyzed using micro-computed tomography (µCT), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and PCR.
• Autophagy dynamic analyses were performed on fetal mesenchyme.

Main Results:

• LP offspring showed reduced body mass but no significant differences in head volume.
• EDS revealed altered calcium and phosphorus percentages in LP fetuses' mandibles and calvaria.
• SEM indicated increased hydroxyapatite deposition on calvaria but delayed mineralization and higher collagen in mandibles of LP fetuses, alongside reduced autophagy and differential gene expression (Akt1, Mtor, Nfkb, Smad1).

Conclusions:

• Gestational protein restriction appears to alter in utero bone differentiation, leading to craniofacial bone development changes.
• Findings suggest delayed mandible mineralization and altered autophagy in response to maternal protein deficiency.
• Results contribute to understanding the Developmental Origins of Health and Disease (DOHaD) concerning craniofacial structures.