Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts

Abstract

Background: Fibrosis is an important histological change occurring in preeclamptic placentas, and might depends on the excess deposition of collagen I. However, the role of fibrotic placentas and collagen I in the pathogenesis of preeclampsia remains unclear. Methods: Collagen deposition and the expression of Collagen I in human placentas were analysed by Masson staining, Sirius red staining and western blotting. The role of collagen I in preeclampsia pathogenesis was studied in C57BL/6 mice.HTR-8/SVneo cells were used to investigate the mechanisms underlying the effects of collagen I in trophoblasts by transcriptome sequencing and pharmacological agonists. Finding: Human preeclamptic placentas exhibited a higher degree of fibrosis in stem villi and terminal villi than normal placentas, and were characterized by collagen I deposition. In vivo, a single injection of collagen I on gestational day 0.5 led to an increase in systolic pressure of pregnant mice from gestational day 4.5 -17.5, to a decrease in weight and number of viable embryos, and to enhanced placental collagen I expression, and degree of fibrosis compared with control mice. In vitro, collagen I attenuated the proliferation and invasion of HTR-8SV/neo cells. This effect could be reversed by treatment with agonist s of ERK and β-catenin. Transcriptome sequencing demonstrated that pathways related to cell proliferation and invasion were significantly downregulated in HTR-8/SVneo cells. Interpretation: Collagen I induced preeclampsia-like symptoms by suppressing the proliferation and invasion of trophoblasts through inhibition of the ERK phosphorylation and WNT/β-catenin signalling pathways. Funding: National Natural Science Foundation of China and Guangdong Province. Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: The collection of placentas was approved by the Ethics Committee of Nanfang Hospital（NFEC-2017-055）. All participants gave written consent prior to donating their placenta.