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PSG7 and 9 (Pregnancy-Specific β-1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia
Manju Kandel1,2, Teresa M MacDonald2,3, Susan P Walker2,3
1Translational Obstetrics Group Mercy Hospital for Women Heidelberg Victoria Australia.
Insights
Pregnancy-specific glycoproteins 7 and 9 (PSG7 and PSG9) show increased levels before preeclampsia onset and in established cases. Placental inflammation may drive their release, suggesting potential as predictive biomarkers for preeclampsia.
Area of Science:
- Reproductive biology
- Maternal-fetal medicine
- Biomarker discovery
Background:
- Preeclampsia is a pregnancy-specific condition characterized by significant maternal endothelial dysfunction.
- Currently, there is a lack of reliable predictive biomarkers for preeclampsia.
- Pregnancy-specific β-1 glycoproteins (PSGs), including PSG7 and PSG9, are potential candidates for investigation.
Purpose of the Study:
- To evaluate the biomarker potential, expression, and function of PSG7 and PSG9 in preeclampsia.
- To determine if PSG7 and PSG9 levels change before preeclampsia onset and correlate with disease severity.
Main Methods:
- Analysis of PSG7 and PSG9 levels in Australian and UK cohorts at different gestational ages, including high-risk pregnancies.
- Validation in plasma and placental samples from patients with established preeclampsia and in a South African cohort stratified for disease severity (PROVE cohort).
- In vitro studies using syncytialized cytotrophoblast stem cells exposed to inflammatory cytokines (TNFα, IL-6) and primary endothelial cells treated with recombinant PSGs.
Main Results:
- Significantly increased circulating levels of PSG7 and PSG9 were observed at 36 weeks gestation preceding term preeclampsia diagnosis in Australian cohorts.
- Elevated PSG7 and PSG9 levels were also detected in high-risk pregnancies (28-32 weeks gestation) and in patients with established preeclampsia (<34 weeks gestation).
- PSG7 and PSG9 levels were elevated in patients with severe preeclampsia features (PROVE cohort), and inflammatory cytokines increased their expression and secretion in cytotrophoblast cells.
Conclusions:
- Circulating PSG7 and PSG9 are elevated before preeclampsia onset and in established disease, indicating their potential as predictive biomarkers.
- Placental inflammation, stimulated by cytokines like TNFα and IL-6, may be responsible for the increased production and release of PSG7 and PSG9.
- While PSG7 and PSG9 show promise as biomarkers, their direct functional impact on endothelial dysfunction markers appears modest.
Abstract:
Background Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy-specific β-1 glycoprotein 7) and PSG9 (pregnancy-specific β-1 glycoprotein 9) in preeclampsia. Methods and Results At 36 weeks gestation preceding term preeclampsia diagnosis, PSG7 and PSG9 (in Australian cohorts of n=918 and n=979, respectively) were significantly increased before the onset of term preeclampsia (PSG7, P=0.013; PSG9, P=0.0011). In samples collected at 28 to 32 weeks from those with preexisting cardiovascular disease and at high risk of preeclampsia (Manchester Antenatal Vascular Service, UK cohort, n=235), both PSG7 and PSG9 were also significantly increased preceding preeclampsia onset (PSG7, P<0.0001; PSG9, P=0.0003) relative to controls. These changes were validated in the plasma and placentas of patients with established preeclampsia who delivered at <34 weeks gestation (PSG7, P=0.0008; PSG9, P<0.0001). To examine whether PSG7 and PSG9 are associated with increasing disease severity, we measured them in a cohort from South Africa stratified for this outcome, the PROVE (Preeclampsia Obstetric Adverse Events) cohort (n=72). PSG7 (P=0.0027) and PSG9 (P=0.0028) were elevated among patients who were preeclamptic with severe features (PROVE cohort), but not significantly changed in those without severe features or with eclampsia. In syncytialized first trimester cytotrophoblast stem cells, exposure to TNFα (tumor necrosis factor α) or IL-6 (interleukin 6) significantly increased the expression and secretion of PSG7 and PSG9. In contrast, when we treated primary endothelial cells with recombinant PSG7 and PSG9, we only observed modest changes in Flt-1 (FMS-like tyrosine kinase-1) expression and Plgf (placental growth factor) expression, and no other effects on proangiogenic/antiangiogenic or endothelial dysfunction markers were observed. Conclusions Circulating PSG7 and PSG9 are increased before preeclampsia onset and among those with established disease with their production and release potentially driven by placental inflammation.
