Impact of Early Postnatal Maternal Separation Stress on Pancreatic Function in Rodents: A Systematic Review and Meta-Analysis

Abstract

Early postnatal stress is a critical factor in metabolic programming. Maternal separation (MS) in rodents, a widely validated model, has been linked to pancreatic alterations. This systematic review and meta-analysis aimed to evaluate the effect of MS on pancreatic morphology and function in rodents. This review followed the PRISMA and SYRCLE guidelines, with a protocol registered in PROSPERO (CRD420251004633). Experimental studies in rodents comparing MS with standard rearing, which reported pancreatic morphofunctional and metabolic parameters, were included. A comprehensive search was performed in the Web of Science, Embase, Medline, Scopus, BIREME-BVS, and SciELO databases until March 2025, without language restrictions. Extracted data included glucose, insulin, insulin sensitivity indices (QUICKI, HOMA), and glucose tolerance tests (GTTs). Meta-analyses were performed using random-effects models, and subgroup analyses were applied to explore sources of heterogeneity. Of 491 references, 25 studies were included in the meta-analysis, which showed that MS was associated with significantly higher glucose levels (SMD −0.41; 95% CI: −0.71 to −0.11) and worse GTT response (SMD −1.02; 95% CI: −1.23 to −0.82). Furthermore, the QUICKI index was significantly decreased (SMD 0.75; 95% CI: 0.14 to 1.35), indicating insulin resistance. MS in rodents induces pancreatic alterations associated with insulin resistance and glucose intolerance, suggesting that early stress could program long-term metabolic vulnerability.