Lucas, Edralin A.Chandrashekar, Ranjitha Hubbanahalli2024-11-272024-11-272024-07https://hdl.handle.net/20.500.14446/345702Objective: Early life factors have been shown to play a role in child health and development and stress is one of the factors that could have major impact on host health. Thus, our objective was to investigate chronic early life stress (CES) impact on bone development, mineralization, and microarchitecture at various postnatal stages using rat model. Methods: Pregnant Sprague-Dawley rats were subjected to a limited bedding and nesting model to induce CES. The offspring were assessed at PND 10, 21, and 35. Tibial length as well as tibial and lumbar (L4) BMD, BMC, and bone mineral area (BMA) were measured using dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was examined using microcomputed tomography (μCT). Changes in gene expression from the L4 vertebra were analyzed by RNA sequencing. Statistical analysis was performed using two-way ANOVA with CES and sex as factors. P < 0.05 was considered statistically significant. Results: At PND 10, there were no significant differences in BMD and BMC between the treatment groups, but tibial length was significantly decreased by CES. By PND 21, BMC and tibial area were significantly reduced in the CES group, indicating impaired bone mineral accumulation. At PND35, tibial length remained significantly reduced by CES, while BMD and BMC differences were less affected. L4 vertebral BMA and BMC were all reduced by CES. μCT analysis of tibial cortical bone showed significant changes in cortical thickness and bone volume at PND10 and 21, respectively. For the L4 vertebra, μCT data indicated significant increases in the degree of anisotropy and structural model index at PND21 and 35, respectively. Transcriptome analyses revealed significant differential expression of genes involved in immune response, cellular repair, and stress adaptation at PND 21 but not at PD10 and PD35. Conclusion: CES significantly disrupts BMC, BMD, length and microarchitecture differently at various stages of postnatal development. Transcriptome analyses suggests that these changes are mediated by alterations in gene expression related to immune function and cellular repair. Future research should focus on tracking the longitudinal impacts of CES on bone health from infancy into adulthood, and exploring nutritional interventions, stress reduction programs, and molecular studies that can mitigate the negative effects of CES on bone.application/pdfCopyright is held by the author who has granted the Oklahoma State University Library the non-exclusive right to share this material in its institutional repository. Contact Digital Library Services at lib-dls@okstate.edu or 405-744-9161 for the permission policy on the use, reproduction or distribution of this material.Thesis