Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36 weeks’ gestation (n = 1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24–34 weeks’ gestation); two prospective cohorts collected on the day of delivery (36 + 3–41 + 3 weeks’ gestation, n = 562 and n = 405 respectively) and a cohort who delivered for preterm FGR (< 34 weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses.
Bibliographical noteFunding Information:
Funding for this work was provided by the National Health and Medical Research Council (#1065854, #1183854, #116071), an Australian Government Research Training Program Scholarship, and RANZCOG Taylor Hammond Scholarship to TM; National Health and Medical Research Council Fellowships to TKL (#1159261), NJH (#1146128), ST (#1136418). The funders played no role in study design or analysis.
from the RIKEN BRC through the National BioResource Project of the MEXT/AMED, Japan and cultured according to the publication from Okae and colleagues28. Syncytiotrophoblasts were differentiated from cyto-trophoblasts as previously described28.
© 2021, The Author(s).