Preeclampsia is a serious pregnancy-induced disorder unique to humans affecting 4.6% of pregnancies worldwide. Advances in the detection, prevention and treatment of preeclampsia have been poor due to our inadequate understanding of its pathogenesis. Here, we performed a proteomics study on isolated primary pregnancy placental fibroblasts treated with siRNA against COL1A2. Loss of COL1A2 in placental fibroblasts significantly dysregulated 74 proteins (39 upregulated, 35 downregulated), which were enriched for pathways including ECM remodeling/wound healing, coagulation and fibrinolysis. Our study provides critical insight into the early pregnancy dysfunction underlying preeclampsia, opening up new avenues for predictive biomarker and preventative treatment discovery.