(120) Placental Expression of Stanniocalcin 2 (STC2) in Healthy and Preeclamptic Pregnancies

Thursday, February 9, 2023

10:30 AM – 12:00 PM

Objective: Stanniocalcin 2 (STC2) is a newly discovered component of the growth hormone-insulin-like growth factor (IGF) axis shown to potently inhibit the proteolytic activity of PAPP-A2. The IGF-axis is an important regulator of placental and fetal growth and levels of plasma and placental PAPP-A2 are elevated in preeclamptic (PE) pregnancies. Given the protein expression of STC2 in the placenta and PE is not known, we sought to determine the expression of STC2 to evaluate its potential role in placental development and PE.

Study Design: Chorionic villi (CV) and basal plate (BP) samples were obtained under IRB approved studies. Available paired CV and BP samples (n=6; 18-40 wk) and BP from pregnancies complicated by PE (n=19; 24-40 wk) and gestational age (GA) matched normotensive pregnancies (CTL) (n=19; 25-40 wk) were used. Formalin-fixed tissue sections were stained for CK7, HLA-G and STC2. STC2 immunoblot was performed on protein lysates.

Results: Immunohistochemistry detected STC2 expression in the human placental tissue predominately in the invasive cytotrophoblasts (EVT) and syncytiotrophoblasts (STB). By immunoblot, STC2 expression was significantly higher in the BP (median [IQR], 0.080 [0.010-0.177]) than CV (0.000 [0.000-0.012], p< 0.01). There was no significant difference in the STC2 expression in BP from PE (0.101 [0.027-0.218]) compared to CTL (0.058 [0.009-0.154], p=0.21) (Fig. 1). SCT2 levels over GA and by condition did not show a significant correlation (All: r=0.07, p=0.69; PE: r=0.22, p=0.36; CTL: r=-0.06, p=0.79) (Fig. 2). Large interindividual variation in expression levels was observed.

Conclusion: We report for the first time that STC2 shows spatial regulation in the placenta with higher protein expression in BP than CV, suggesting STC2 plays a role in the IGF-axis particularly in the BP region of the placenta. The variation in expression levels and lack of difference in PE indicates that factors other than GA or PE impact expression. Further studies are needed to determine the role of STC2 in trophoblast function and identify factors that regulate STC2 expression in the placenta.

Primary & Presenting Author(s)

Anna Sophie L. Kjaer, MD (she/her/hers)
Stanford University
Palo Alto, California, United States

Coauthor(s)

SS
Shilpi Sehgal, PhD
Stanford University
Palo Alto, California, United States
Yanming Wu, MD (she/her/hers)
Postdoc researcher
Stanford University
Palo Alto, California, United States
PI
Purnima Iyer, PhD
Stanford University
Palo Alto, California, United States
VW
Virginia D. Winn, MD
Stanford University
Palo Alto, California, United States