mhdegnes

• Sellevoll, Hilde Bastøe; Andresen, Ina Jungersen; Westerberg, Ane Cecilie; Degnes, Maren-Helene Langeland; Ueland, Thor & Zucknick, Manuela [Show all 7 contributors for this article] (2026). Placental Protein Release and Uptake From the Fetal Circulation in Healthy Term Pregnancies—A Human In Vivo Exploratory Study. The FASEB Journal. ISSN 0892-6638. 40(3). doi: 10.1096/fj.202503626R. Full text in Research Archive
• Westerberg, Ane Cecilie; Degnes, Maren-Helene Langeland; Andresen, Ina Jungersen; Sellevoll, Hilde Bastøe; Lekva, Tove & Ueland, Thor [Show all 11 contributors for this article] (2025). Placenta-Derived Proteins in Preeclampsia: A Human In Vivo Study. Hypertension. ISSN 0194-911X. 82(12), p. 2125–2139. doi: 10.1161/hypertensionaha.125.24886. Full text in Research Archive Show summary

  BACKGROUND: Placental dysfunction, a key feature of preeclampsia, has been linked to altered placental release of proteins into the maternal circulation. However, the identity of placenta-derived proteins in preeclampsia is unclear due to the inaccessibility of the placenta during pregnancy. This study aimed to identify placenta-derived proteins in preeclampsia, characterize their associated biological processes, and assess their biomarker potential. METHODS: We used the 4-vessel sampling method to collect blood from the ingoing and outgoing vessels of the placenta during cesarean section to identify proteins secreted from the placenta. Prospectively collected samples from a separate pregnancy cohort were also included. Proteins were quantified on the SomaLogic 5000-plex platform. RESULTS: We identified 620 placenta-derived proteins, including 229 proteins released in both healthy pregnancies and in preeclampsia, 345 proteins released in preeclampsia only, and 46 proteins released in healthy controls only. Biological process gene ontologies linked to oxidative stress and cellular turnover were enriched among the placenta-derived proteins in preeclampsia, but not in healthy pregnancies. In the prospective cohort, 21 of the 620 placenta-derived proteins had altered levels in preeclampsia at least 3 weeks before, and on average >7 weeks before delivery. Among these, prediction performance for preeclampsia was promising for 11 biomarker candidates in single protein models (area under the curve >0.7) and 17 significantly improved prediction when combined with clinical variables as compared with a clinical model alone. CONCLUSIONS: Using a unique in vivo sampling method, we identified placenta-derived proteins in preeclampsia, several of which showed promising biomarker potential.

• Andresen, Ina Jungersen; Zucknick, Manuela; Degnes, Maren-Helene Langeland; Angst, Martin S.; Aghaeepour, Nima & Romero, Roberto [Show all 10 contributors for this article] (2024). Prediction of late-onset preeclampsia using plasma proteomics: a longitudinal multi-cohort study. Scientific Reports. 14(1). doi: 10.1038/s41598-024-81277-2. Full text in Research Archive Show summary

  Preeclampsia is a pregnancy disorder with substantial perinatal and maternal morbidity and mortality. Pregnant women at risk of preeclampsia would benefit from early detection for follow-up, timely interventions and delivery. Several attempts have been made to identify protein biomarkers of preeclampsia, but findings vary with demographics, clinical characteristics, and time of sampling. In the current study, we combined three independent longitudinal pregnancy cohorts (Detroit, Stanford and Oslo) resulting in 124 late-onset preeclampsia (LOPE) cases and 178 gestational age matched controls, and analyzed > 1000 proteins in maternal plasma sampled between 12 and 34 weeks of gestation. Differential abundance analysis of combined protein data revealed increased deviation in protein abundance trajectories throughout gestation in women destined to develop LOPE compared to controls. There were no differentially abundant proteins at time interval T1 (12–19 weeks), yet 31 differentially abundant proteins were found at time interval T2 (19–27 weeks), and 48 proteins at time interval T3 (27- 34 weeks). Multi-protein random forest models assessed via cross-validation predicted LOPE with an area under the ROC curve of 0.72 (0.65–0.78), 0.76 (0.71–0.81) and 0.80 (0.75–0.85) at time interval T1, T2 and T3, respectively. The results at T3 were confirmed using a leave-one-cohort-out analysis suggesting cross-cohort consistency, and at T1 and T2 when the largest two cohorts were used as training sets.

• Degnes, Maren-Helene Langeland; Westerberg, Ane Cecilie; Andresen, Ina Jungersen; Henriksen, Tore; Roland, Marie Cecilie & Zucknick, Manuela [Show all 7 contributors for this article] (2024). Protein biomarker signatures of preeclampsia - a longitudinal 5000-multiplex proteomics study. Scientific Reports. 14(1). doi: 10.1038/s41598-024-73796-9. Full text in Research Archive Show summary

  We aimed to explore novel biomarker candidates and biomarker signatures of late-onset preeclampsia (LOPE) by profiling samples collected in a longitudinal discovery cohort with a high-throughput proteomics platform. Using the Somalogic 5000-plex platform, we analyzed proteins in plasma samples collected at three visits (gestational weeks (GW) 12–19, 20–26 and 28–34 in 35 women with LOPE (birth ≥ 34 GW) and 70 healthy pregnant women). To identify biomarker signatures, we combined Elastic Net with Stability Selection for stable variable selection and validated their predictive performance in a validation cohort. The biomarker signature with the highest predictive performance (AUC 0.88 (95% CI 0.85–0.97)) was identified in the last trimester of pregnancy (GW 28–34) and included the Fatty acid amid hydrolase 2 (FAAH2), HtrA serine peptidase 1 (HTRA1) and Interleukin-17 receptor C (IL17RC) together with sFLT1 and maternal age, BMI and nulliparity. Our biomarker signature showed increased or similar predictive performance to the sFLT1/PGF-ratio within our data set, and we were able to validate the biomarker signature in a validation cohort (AUC ≥ 0.90). Further validation of these candidates should be performed using another protein quantification platform in an independent cohort where the negative and positive predictive values can be validly calculated.

• Westerberg, Ane Cecilie; Degnes, Maren-Helene Langeland; Andresen, Ina Jungersen; Roland, Marie Cecilie & Michelsen, Trond Melbye (2024). Angiogenic and vasoactive proteins in the maternal-fetal interface in healthy pregnancies and preeclampsia. American Journal of Obstetrics and Gynecology. ISSN 0002-9378. 231(5), p. 550.e1–550.e22. doi: 10.1016/j.ajog.2024.03.012. Full text in Research Archive Show summary

  Background Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to the pathophysiology. The contribution of the placenta as a source of these factors remains unclear. Furthermore, little is known about fetal angiogenic and vasoactive proteins and the relation between maternal and fetal levels. Objective We describe placental growth factor, soluble Fms-like tyrosine kinase 1, soluble endoglin, and endothelin 1–3 in 5 vessels in healthy pregnancies, early- and late-onset preeclampsia. Specifically, we aimed to (1) compare protein abundance in vessels at the maternal-fetal interface between early- and late-onset preeclampsia, and healthy pregnancies, (2) describe placental uptake and release of proteins, and (3) describe protein abundance in the maternal vs fetal circulations. Study Design Samples were collected from the maternal radial artery, uterine vein and antecubital vein, and fetal umbilical vein and artery in 75 healthy and 37 preeclamptic mother-fetus pairs (including 19 early-onset preeclampsia and 18 late-onset preeclampsia), during scheduled cesarean delivery. This method allows estimation of placental release and uptake of proteins by calculation of venoarterial differences on each side of the placenta. The microarray-based SomaScan assay quantified the proteins. Results The abundance of soluble Fms-like tyrosine kinase 1 and endothelin 1 was higher in the maternal vessels in preeclampsia than in healthy pregnancies, with the highest abundance in early-onset preeclampsia. Placental growth factor was lower in the maternal vessels in early-onset preeclampsia than in both healthy and late-onset preeclampsia. Maternal endothelin 2 was higher in preeclampsia, with late-onset preeclampsia having the highest abundance. Our model confirmed placental release of placental growth factor and soluble Fms-like tyrosine kinase 1 to the maternal circulation in all groups. The placenta released soluble Fms-like tyrosine kinase 1 into the fetal circulation in healthy and late-onset preeclampsia pregnancies. Fetal endothelin 1 and soluble Fms-like tyrosine kinase 1 were higher in early-onset preeclampsia, whereas soluble endoglin and endothelin 3 were lower in both preeclampsia groups than healthy controls. Across groups, abundances of placental growth factor, soluble Fms-like tyrosine kinase 1, and endothelin 3 were higher in the maternal artery than the fetal umbilical vein, whereas endothelin 2 was lower. Conclusion An increasing abundance of maternal soluble Fms-like tyrosine kinase 1 and endothelin 1 across the groups healthy, late-onset preeclampsia and early-onset combined with a positive correlation may suggest that these proteins are associated with the pathophysiology and severity of the disease. Elevated endothelin 1 in the fetal circulation in early-onset preeclampsia represents a novel finding. The long-term effects of altered protein abundance in preeclampsia on fetal development and health remain unknown. Further investigation of these proteins’ involvement in the pathophysiology and as treatment targets is warranted.

• Degnes, Maren-Helene Langeland; Westerberg, Ane Cecilie; Zucknick, Manuela; Powell, Theresa L.; Jansson, Thomas & Henriksen, Tore [Show all 8 contributors for this article] (2022). Placenta-derived proteins across gestation in healthy pregnancies—a novel approach to assess placental function? BMC Medicine. 20. doi: 10.1186/s12916-022-02415-z. Full text in Research Archive Show summary

  ackground Placenta-derived proteins in the systemic maternal circulation are suggested as potential biomarkers for placental function. However, the identity and longitudinal patterns of such proteins are largely unknown due to the inaccessibility of the human placenta and limitations in assay technologies. We aimed to identify proteins derived from and taken up by the placenta in the maternal circulation. Furthermore, we aimed to describe the longitudinal patterns across gestation of placenta-derived proteins as well as identify placenta-derived proteins that can serve as reference curves for placental function. Methods We analyzed proteins in plasma samples collected in two cohorts using the Somalogic 5000-plex platform. Antecubital vein samples were collected at three time points (gestational weeks 14–16, 22–24, and 30–32) across gestation in 70 healthy pregnancies in the longitudinal STORK cohort. In the cross sectional 4-vessel cohort, blood samples were collected simultaneously from the maternal antecubital vein (AV), radial artery (RA), and uterine vein (UV) during cesarean section in 75 healthy pregnancies. Placenta-derived proteins and proteins taken up by the placenta were identified using venoarterial differences (UV-RA). Placenta-derived proteins were defined as placenta-specific by comparison to the venoarterial difference in the antecubital vein-radial artery (AV-RA). These proteins were described longitudinally based on the STORK cohort samples using a linear mixed effects model per protein. Using a machine learning algorithm, we identified placenta-derived proteins that could predict gestational age, meaning that they closely tracked gestation, and were potential read-outs of placental function. Results Among the nearly 5000 measured proteins, we identified 256 placenta-derived proteins and 101 proteins taken up by the placenta (FDR < 0.05). Among the 256 placenta-derived proteins released to maternal circulation, 101 proteins were defined as placenta-specific. These proteins formed two clusters with distinct developmental patterns across gestation. We identified five placenta-derived proteins that closely tracked gestational age when measured in the systemic maternal circulation, termed a “placental proteomic clock.”

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• Degnes, Maren-Helene Langeland; Westerberg, AC; Andresen, Ina Jungersen; Zucknick, Manuela; Powell, Theresa L & Jansson, Thomas [Show all 9 contributors for this article] (2022). Six placenta-derived proteins as markers of placental function. Full text in Research Archive
• Andresen, Ina Jungersen; Degnes, Maren-Helene Langeland; Zucknick, Manuela; Powell, Theresa L; Jansson, Thomas & Henriksen, Tore [Show all 8 contributors for this article] (2022). Protein biomarkers of late-onset preeclampsia. Full text in Research Archive

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