Watermelon‐Derived Extracellular Vesicles Influence Human Ex Vivo Placental Cell Behavior by Altering Intestinal Secretions

Abstract

Scope: During pregnancy, mother-to-fetus transfer of nutrients is mediated by the placenta; sub-optimal placental development and/or function results in fetal growth restriction (FGR), and the attendant risk of stillbirth, neurodevelopmental delay, and non-communicable diseases in adulthood. A maternal diet high in fruit and vegetables lowers the risk of FGR but the association cannot be explained fully by known macro-and micronutrients. Methods and results: This study investigates if dietary-derived extracellular vesicles (EVs) can regulate placental function. The study characterizes the microRNA and protein cargo of EVs isolated from watermelon, show they are actively internalized by human intestinal epithelial cells in vitro, use mass spectrometry to demonstrate that they alter the intestinal secretome and bioinformatic analyses to predict the likely affected pathways in cells/tissues distal to gut. Application of the watermelon EV-modified intestinal secretome to human placental trophoblast cells and ex vivo tissue explants affects the trophoblast proteome and key aspects of trophoblast behavior, including migration and syncytialization. Conclusion: Dietary-derived plant EVs can modify intestinal communication with distal tissues, including the placenta. Harnessing the beneficial properties of dietary-derived plant EVs and/or exploiting their potential as natural delivery agents may provide new ways to improve placental function and reduce rates of FGR.

Characterization of Nanovesicles Isolated from Olive Vegetation Water

“…Other proteins detected in this study, namely histone H4-like, actin, and heat shock 70 kDa, were already detected in mammal EVs, as verified by a manual search in the Vesiclepedia database (microvesicles.org accessed on 27 March 2023). Notably, 8 out of 19 proteins identified in OVW-NVs (i.e., actin, heat shock 70 kDa, elongation factor Tu, monocopper oxidase, vicilin, PI-PLC X domain-containing protein, chitinase, pathogenesis-related R major form, and ras-related RABB1c) were already detected in NVs isolated from edible plants and fruits, such as citrus juice, grape, lemon, watermelon, ginger, tomato and garlic [ 1 , 2 , 8 , 21 , 22 ].…”

Plant-Derived Extracellular Vesicles: A New Revolutionization of Modern Healthy Diets and Biomedical Applications

“…The isolation of PDEVs begins with the preprocessing steps, including washing samples with ultrapure or deionized water and then manual or automatic processing, depending on the plant part being investigated (Figure a). For example, ginger was washed in ultrapure water, broccoli and ginseng were minced and ground, , mesocarp was removed from watermelon, bitter melon was milled, sweet oranges and asparagus were manually squeezed, , cannabis was homogenized, and blueberries were passed through a metallic strainer . In addition, less succulent plants can be extracted by homogenization in distilled water or phosphate-buffered saline …”

Exploring the Potential of Plant-Derived Exosome-like Nanovesicle as Functional Food Components for Human Health: A Review

“…In addition, PELN also has great potential for protecting the heart [ 13 ], promoting the expression of beneficial genes in the skin [ 96 ], and promoting placental growth and activity [ 91 ], although the mechanism has not yet been revealed ( Table 1 ).…”