Understanding Intracellular Transport Impairments in Maternal Protein Restriction: A Scoping Review of DOHaD-Driven Cellular Biology Perspective

Malnutrition remains a major global socioeconomic challenge. When it occurs during critical developmental windows (pregnancy and lactation), it can impair maternal health and predispose offspring to long-term diseases, a central concept within the Developmental Origins of Health and Disease (DOHaD). Maternal Protein Restriction (MPR) is a widely used experimental model in this field and is known to disrupt multiple organs and systems in the offspring, increasing susceptibility to metabolic disorders. However, the cellular pathways underlying these outcomes remain insufficiently explored, particularly vesicular transport and the endomembrane system. This review examined the effects of MPR on organelles related to vesicular dynamics. Following predefined inclusion and exclusion criteria, 20 PubMed articles were selected, addressing MPR-induced alterations in the cytoskeleton, endoplasmic reticulum (ER), Golgi, endocytosis, and exocytosis. Overall, evidence indicates that MPR disrupts cytoskeletal integrity—affecting actin networks in renal, adipose, muscle, and neural cells. MPR compromises ER and Golgi activities in several organs. In the placenta, endocytic activity was consistently elevated (macropinocytosis). Exocytosis was also perturbed, contributing to lipid accumulation and inflammation. Systemically, MPR altered circulating amino acid levels, impaired hematological parameters, reduced leukocyte migration, and enhanced placental amino acid transport. These findings demonstrate that MPR destabilizes cytoskeletal architecture, ER–Golgi function, and vesicular transport across multiple offspring tissues, identifying the endomembrane system as a critical target of developmental programming. These alterations suggest persistent vulnerabilities in cellular homeostasis. Therefore, we propose the term maternal diet–dependent cellular-vesicular disorders (MDCVD), establishing a conceptual framework for future mechanistic and translational studies.