Chronic glucocorticoid excess during rat pregnancy disrupts placental oxygenation and alters feto-placental vascular architecture.

INTRODUCTION

Prenatal glucocorticoid overexposure causes fetal growth restriction, often mediated by placental vascular dysfunction, yet underlying mechanisms remain poorly defined. This study examined the temporal and spatial progression of placental oxygenation and feto-placental vascular structure following chronic dexamethasone exposure using three-dimensional imaging.

METHODS

Time-mated pregnant Wistar rats received dexamethasone (0.5 μg/mL) or vehicle in drinking water from embryonic day (E) 13-21. Placental oxygenation was evaluated at E15, E18, and E21 using T2∗ magnetic resonance imaging (MRI) during maternal hyperoxia challenge. Feto-placental arterial architecture was assessed at E21 using micro-computed tomography with Microfil® perfusion.

RESULTS

Dexamethasone exposure reduced fetal and placental weights from E18 onward. At E21, micro-CT revealed that placentas exhibited 50% reduction in vascular volume and 30% decrease in vessel segments, with selective loss of arterioles (-42%) and pre-arterioles (-38%) while preserving larger vessels. Terminal vessel branching was significantly reduced. Dexamethasone significantly reduced placental oxygenation (ΔT2∗) at E18 (51%, p < 0.05), through to E21 (55%, p < 0.0001). At E21, comparable reduction in oxygen occurred in both dexamethasone-treated labyrinth (52%) and junctional (54%) zones in comparison to control (both p < 0.001).

DISCUSSION: Chronic glucocorticoid exposure induces placental functional deficits with selective terminal vessel loss in late gestation. This temporal progression links impaired branching angiogenesis to compromised oxygen exchange capacity. These findings advance understanding of placental insufficiency mechanisms and highlight the potential of MRI for early detection of placental dysfunction.