Structural and functional foetal renal abnormalities as a mechanism of oligohydramnios in a guinea pig model of growth restriction.

Abstract

In this study, we aimed to investigate the mechanisms underlying oligohydramnios in foetal growth restriction (FGR), focusing on the contribution of renal structural and functional abnormalities. A guinea pig model of maternal nutrient restriction (MNR) was established to induce FGR. Pregnant guinea pigs were divided into control and MNR groups. Foetuses were classified as appropriate for gestational age (AGA) or FGR based on body weight. Amniotic fluid and foetal kidneys were collected at gestational days 60-61. Amniotic fluid biomarkers were measured. Histopathology was performed to evaluate renal morphology. MNR resulted in a 25% reduction in foetal body and placental weights and a 50% reduction in amniotic fluid volume compared with AGA controls. Histological analyses revealed renal injury in FGR foetuses, characterised by podocyte foot process effacement, endothelial damage, and disruption of the tubular basement membrane. These structural abnormalities indicate impaired glomerular filtration and defective tubular reabsorption. Amniotic fluid concentrations of albumin, cystatin C, and liver-type fatty acid-binding protein were higher in FGR than in controls, reflecting glomerular leakage and tubular oxidative stress. These findings are consistent with reduced foetal urine production and development of oligohydramnios. They indicate that oligohydramnios in MNR-induced FGR is associated with compromised renal integrity.