Oral Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

COL1A2 is down-regulated in early pregnancy placenta from term preeclampsia and is associated with disrupted angiogenesis (#191)

Sarvenaz Sabourirad 1 2 , Leiani Santos 1 2 , Swati Varshney 1 , Teresa So 1 , Wei Zhou 1 2 , Nicholas Williamson 1 , Daniel Rolnik 3 , Fabricio da Silva Costa 4 , Argyro Syngelaki 5 , Kypros Nicolaides 5 , Evdokia Dimitriadis 1 2 , Ellen Menkhorst 1 2
  1. University of Melbourne, North Melbourne, VIC, Australia
  2. Gynecology Research Centre, Royal Women's Hospital, Melbourne, VIC
  3. Monash University, Melbourne, VIC, Australia
  4. Griffith university, Gold Coast, QLD, Australia
  5. Fetal Medicine Foundation, London, UK

Preeclampsia is a hypertensive disorder during pregnancy that endangers both mother and fetus. Term preeclampsia (>37 weeks) constitutes up to 80% of preeclampsia cases in developed countries, yet the underlying etiology is poorly understood. There are no reliable predictors or preventions. Although placental dysfunction is central to preeclampsia pathogenesis, the underlying causes remain unknown. We aimed to investigate early pregnancy placental changes in women who later developed term preeclampsia.
Proteomics analyses were performed on chorionic villus samples (CVS; n=6-8 per group; 11-13 weeks gestation) from pregnancies that later developed term preeclampsia or were normotensive. Proteins that were differentially expressed (DE) between groups were determined (p<0.05, >1.5 fold). Proteomics identified Collagen Type I Alpha 2 Chain (COL1A2) as down-regulated in term preeclampsia CVS. Placental COL1A2 expression was confirmed using immunohistochemistry, RT-qPCR in CVS (n=8/group), placental explants (n=5/group) and placental villous from 1st, 2nd and term placenta (n=6/group). COL1A2 function was investigated using siRNA knockdown in human umbilical vascular endothelial cells (HUVEC) (n=3/group).
COL1A2 immunolocalized to placental villous stromal, endothelial and Hofbauer cells. COL1A2 immunostaining was significantly reduced in CVS from preterm and term preeclampsia compared to normotensive pregnancies (↓2-fold; p<0.05). COL1A2 mRNA in placental villous was increased by hypoxia (2% oxygen; (↑2.4-fold; p<0.05) compared to normoxia (8% oxygen) and decreased across gestation (1st trimester vs term; ↓8-fold; p<0.05). Loss of COL1A2 enhanced HUVEC tube formation (↑2-fold; p<0.05) and VEGFR1 mRNA (↑1.8 fold; p<0.05).
In conclusion, COL1A2 was dysregulated in the early pregnancy placental stromal and vasculature in pregnancies that later developed term preeclampsia. These compartments are poorly investigated in preeclampsia. Our data strongly suggests COL1A2 has a central role in preeclampsia by disrupting placental development and angiogenesis. These findings offer critical insights into early pregnancy placental dysfunction associated with term preeclampsia and pave the way for the development of targeted therapeutics.