In Vivo Effect of a Synthetic Amniotic Fluid on Fetal Lung and Gastrointestinal Tract: A Pre-Clinical Rodent Model.

Abstract

OBJECTIVE: Amnioinfusions in anhydramnios aim to promote fetal lung development, but currently used fluids (Normal Saline [NS], Lactated Ringer's [LR]) fail to mimic the intrauterine environment and increase reactive oxygen species (ROS). We developed a synthetic amniotic fluid (Amnio-well, AW) designed to reduce intrauterine ROS. This study evaluated the pulmonary and gastrointestinal effects of 2 formulations of&#xa0;AW compared with those of NS and LR in a pre-clinical model. METHOD: At gestational age E17.5, pregnant rats underwent amniotic fluid replacement with NS, LR, AW, AW plus epidermal growth factor and transforming growth factor-&#x3b2; (AW++), or sham control. Fetal lungs were harvested at E20.5 for histology, fractional airspace, and blinded pathological evaluation. Surfactant protein (SP-A, SP-B, SP-C) expression and inflammatory gene panels were assessed in lungs and gastrointestinal (GI) tissue. RESULTS: NS and LR lungs demonstrated edema, macrophage infiltration, and reduced airspace (p&#xa0;<&#xa0;0.001). AW improved SP-B and SP-C relative to control, whereas AW++ suppressed SP-B and SP-C (p&#xa0;<&#xa0;0.05). Lung gene profiling showed NS/LR induced alterations in histamines, annexins, and immune recruitment, while AW closely resembled control. GI histology was similar across groups, though NS/LR altered TNF, prostaglandin, and adhesion pathways (p&#xa0;<&#xa0;0.05). CONCLUSION: AW reduced lung inflammation and enhanced surfactant expression compared with NS or LR, with minimal GI effects.