Stress During Lactation: A Hidden Link to Offspring Bone Health.

Early-life resource limitation is one factor that could have a major impact on child health and development. Thus, using a rat model of limited bedding and nesting (LBN), we investigated the postnatal bone development, mineralization, and microarchitecture. Pregnant Sprague-Dawley rats were subjected to a LBN model to induce chronic early-life stress (CES), while a control group was maintained under standard conditions. The offspring were assessed at postnatal day (PND) 10, 21, and 35. Tibial length was measured, and tibial and lumbar vertebral bone mineral density (BMD), content (BMC), and area (BMA) were assessed using dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was examined using microcomputed tomography (μCT). Changes in gene expression from the lumbar vertebrae were analyzed by transcriptome. 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, tibial BMC and BMA were significantly reduced in the CES group, indicating impaired bone mineral accumulation. At PND 35, tibial length remained significantly reduced by CES, while BMD and BMC differences were less affected. Vertebral BMA and BMC were reduced by CES. μCT analysis of tibial cortical bone showed significant changes in cortical thickness and bone volume at PND 10 and 21, respectively. For the lumbar vertebrae, μCT data indicated significant increases in the degree of anisotropy and structural model index at PND 21 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 PND 10 and PND 35. CES significantly disrupts BMC, BMD, length, and microarchitecture differently at various stages of postnatal development. Transcriptome analyses suggest 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.