Hypoxia-induced stanniocalcin-1 (Stc1) is upregulated in mouse aorta during late pregnancy: Regulation of STC1 in endothelial cells and BeWo trophoblasts

Maternal cardiovascular remodeling is an important adaptation to pregnancy. To characterize molecular changes in the vasculature of pregnant mice, RNA-sequencing of thoracic aortas from pregnant mice at 18 days post-conception (dpc) and non-pregnant controls was performed. Here, we investigate the role and regulation of stanniocalcin-1 ( STC1 ), one of the genes found to be upregulated in the aorta during late pregnancy. Quantitative real-time PCR confirmed that STC1 gene expression in the aorta increases by 12.5 dpc and decreases by postpartum day 2. To investigate potential signals regulating STC1, we cultured human umbilical vein endothelial cells (HUVECs). We found that HUVECs subjected to the chemical hypoxia mimetic deferoxamine (DFX) (50 µM for 24 hours) increased STC1 gene expression in response to this stress. Because STC1 is also expressed in reproductive tissues, we further examined the role and regulation of STC1 in a human placental cell model called BeWo trophoblasts. We hypothesized that upregulation of STC1 in BeWo trophoblasts guards against hypoxic stress and helps regulate pathways of proper placental development. We found DFX (50 µM, 24–48 hours) upregulated STC1 in BeWo cells, reinforcing the connection between STC1 and cellular responses under low-oxygen conditions. In addition to playing a protective role in pathological hypoxia, STC1 may also participate in the normal process of trophoblast fusion, which is critical for placental development. To examine this property in BeWo cells, we treated cells with forskolin (50 µM, 24-48 hours), which activates cell signaling pathways responsible for fusion. Finally, to probe STC1’s effects as a secreted signal, we generated a plasmid expression vector to overexpress STC1 and assess its impact in a non-cell autonomous manner. Our findings suggest that STC1 supports maternal cardiovascular adaptations and protects against hypoxia-related complications. Understanding the role of STC1 in pregnancy may provide insight into maternal-fetal communication and potential therapeutic targets for preeclampsia. Funding provided by Williams College This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.