Organ development in growth-restricted fetuses in the reduced uterine perfusion pressure rat model: A vascular approach of brain, heart, and kidney

Abstract

Fetal growth restriction (FGR) increases the risk of developing cardiovascular, renal, and neurovascular diseases. An overlapping vascular pathophysiology as a response to chronic hypoxia and circulatory redistribution in utero, might underlie this lifelong burden. This study aims to assess potential vascular detoriations in multiple organs following FGR using the Reduced Uterine Perfusion Pressure (RUPP) rat model. The fetal brain, heart, and kidney were collected (RUPP n = 16 vs. sham n = 13) at embryonic day (E)19 for histological assessment of various aspects of vascular and structural development. Results indicated similar microvascularisation in all organs between the groups. Structural assessment demonstrated a decreased brain area and thickness of the somatosensory cortex and thicker right ventricular wall of the heart (not driven by increased proliferation) in RUPP fetuses, and no differences in renal development. In conclusion, the fetal stage might be too early to detect detoriation in organ vasculature, while this study did reveal subtle alterations in structural development of mostly the brain, followed by the heart with sparing of the kidneys. Potentially compensatory mechanisms may be at play at this fetal stage. Nevertheless, small subclinical adaptations could make the FGR offspring more susceptible for second hits with manifestation at older age.