The Role of Acid Sphingomyelinase in Murine Placental Development

Sphingolipids are a diverse class of bioactive signaling lipids that control an array of fundamental cellular processes. Recently, dysregulation of sphingolipid metabolism has been observed in placentas from complicated pregnancies. In the present study, we demonstrate that acid sphingomyelinase (Smpd1), an enzyme involved in sphingolipid metabolism, is critical for normal placental development, and that its deficiency results in fetal/intrauterine growth restriction (IUGR). Smpd1-/- placentas display several structural abnormalities, including a reduced labyrinth compartment and increased thickness of the fetal-maternal interhemal membrane. In addition, Smpd1-/- placentas exhibit a three-fold decrease in sphingosine-1-phosphate (S1P), a sphingolipid important for promoting angiogenesis. Finally, we observed several hallmarks of defective autophagy and lysosomal impairment in Smpd1-/- placentas, which could contribute to the IUGR phenotype. This study proposes Smpd1-deficient mice as a novel model of IUGR, and can aid in the understanding of molecular events which lead to IUGR and placental pathologies in humans.M.Sc.2019-11-15 00:00:0