Overexpression of TLR7 contributes to the development of preeclampsia through suppression of the PI3K-Akt signaling pathway.

Objective: This study aims to uncover key genes contributing to preeclampsia development and elucidate their underlying mechanisms.

Methods: We conducted transcriptome analysis of placental tissues from preeclampsia patients and healthy pregnancies. Pregnant mice were administered a TLR7 agonist to induce preeclampsia-like symptoms. Additionally, we over-expressed TLR7 in HTR8/Svneo cells to assess its effects on cell functions. Co-analysis of transcriptomic differences between TLR7 agonist-treated mice, oe-TLR7 cells, and corresponding control groups was performed to identify key regulatory pathways.

Results: Our findings revealed that the Toll-like receptor (TLR) signaling pathway may serve as a central network hub, with TLR7 being the only significantly altered TLR between preeclampsia and healthy pregnancies. In-vivo studies showed that TLR7 agonist administration in pregnant mice induced preeclampsia -like symptoms, including elevated blood pressure and increased levels of sFlt and sEng. In-vitro experiments demonstrated that over-expression of TLR7 in HTR8/Svneo cells resulted in reduced cell proliferation and migration. Transcriptomic analysis identified the PI3K-Akt signaling pathway as a central regulator that significantly altered following TLR7 over-expression. Activation of the P53 signaling pathway and decreased expression of THBS2/col-IV were found to be potentially regulated by PI3K-Akt signals, further suppressing trophoblast migration and invasion. These effects contribute to superficial placental implantation and compromised uterine perfusion, ultimately leading to the development of preeclampsia.

Conclusion: Our study suggests that the over-activation of TLR7 may play a significant role in preeclampsia development and could be a potential therapeutic target, providing a theoretical basis for the development of novel treatments for preeclampsia.