Hypoxia‐Induced Syndecan 1 Shedding in Placental Trophoblasts is Associated with Increased Peroxide

Preeclampsia is one of the most common obstetrical disorders, affecting ~5% of pregnancies. It is one of the leading causes of maternal and fetal morbidity and mortality, as well as premature birth. While the origins of preeclampsia are obscure, it is believed that many cases are due to placental insufficiency and resulting ischemia/hypoxia. While many of the factors released by the ischemic placenta are known, the full scope of the molecular effects of ischemia on the placenta are not known. We have recently demonstrated that hypoxia causes shedding of the placental extra cellular matrix in vitro and in vivo , particularly the glycoprotein syndecan 1. It has also been reported that vascular ECM shedding can be affected by reactive oxygen species. Therefore, we wished to test the hypothesis that oxidative stress is the mediator of placental syndecan 1. We treated placental trophoblast derived cells (BeWo) for 24 hours with oxygen conditions mimicking healthy (8%) or ischemic (1%) placentas. To determine the effect of hypoxia on peroxide production, we used the peroxide indicator amplex red. In response to hypoxic conditions, amplex fluorescence was significantly increased (6728 ± 196 vs 8201 ± 501 AU, p<0.05), which was attenuated with the peroxide scavenger apocynin (4626 ± 100 AU, p>0.05). In response to hypoxia, SDC1 released from BeWos increased significantly (175 ± 10 vs 280 ± 13 pg/ml, p<0.05). There was no effect of the peroxide scavenger apocynin in normoxic conditions, but there was a significant reduction (185 ± 10 pg/ml, p<0.05) in hypoxic conditions. These data suggest that peroxide is a key mediator of hypoxia‐induced shedding of SDC‐1, and could play a key role in ECM shedding in placental ischemia in vivo. Future studies will examine the in vivo effects of peroxide scavenging on SDC shedding as well as its effects on other ECM components. Support or Funding Information This work was supported in part by NIH grants P01HL51971, P20GM104357, and R01HL137791