Stress during lactation: a hidden link to offspring bone health

Authors: CHANDRASHEKAR, RANJITHA - Oklahoma State University; MULAKALA, BHARATH - Texas A&M University; Gurung, Manoj; VENNA, GEETANJALI - Arkansas Children'S Nutrition Research Center (ACNC); Rearick, Jolene; Onyekweli, Brenda; Ruebel, Meghan; Dado-Fox, Jasmine; ZELEDON, JASMINA - University Arkansas For Medical Sciences (UAMS); TALATALA, RACHELANNE - Arkansas Children'S Nutrition Research Center (ACNC); RODRIGUEZ, KAYLEIGH - University Arkansas For Medical Sciences (UAMS); BISHOP, LAURA - University Arkansas For Medical Sciences (UAMS); SMITH, BRENDA - Indiana University School Of Medicine; STEPHENS, KIMBERLY - University Arkansas For Medical Sciences (UAMS); LUCAS, EDRALIN - Oklahoma State University; Yeruva, Venkat

Submitted to: Calcified Tissue International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/18/2025
Publication Date: 5/30/2025
Citation: Chandrashekar, R., Mulakala, B.K., Gurung, M., Venna, G., Rearick, J.R., Onyekweli, B.I., Ruebel, M., Dado-Fox, J.M., Zeledon, J.A., Talatala, R., Rodriguez, K., Bishop, L., Smith, B., Stephens, K., Lucas, E., Yeruva, V. 2025. Stress during lactation: a hidden link to offspring bone health. Calcified Tissue International. 116(2025).Article 79. https://doi.org/10.1007/s00223-025-01378-6.
DOI: https://doi.org/10.1007/s00223-025-01378-6

Interpretive Summary: Early life stress is one factor that could have a major impact on child health and development. Thus, using a rodent model, we investigated the impact of chronic early life stress (CES) on postnatal bone development. CES significantly disrupts bone mineral content, bone mineral density, length and microarchitecture differently at various stages of postnatal development. Transcriptome analyses revealed significant differential expression of genes involved in immune response, cellular repair, and stress adaptation at postnatal day (PND) 21 but not at PND10 and PND35. 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.

Technical Abstract: Early life stress is one factor that could have a major impact on child health and development. Thus, using a rat model, we investigated the impact of chronic early life stress (CES) on postnatal bone development, mineralization, and microarchitecture. Pregnant Sprague-Dawley rats were subjected to a limited bedding and nesting (LBN) model to induce CES, while a control group was maintained under standard conditions to allow for comparison. 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, BMC and tibial BMA 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. 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 lumbar vertebrae, 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 PND10 and PND35. 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.