hsa_circ_0003218 Mitigates Trophoblast Dysfunction in Gestational Diabetes by Regulating TLR4/MyD88/NF-κB and NLRP3 Inflammasome.

BACKGROUND

This investigation sought to determine hsa_circ_0003218's role and mechanism in trophoblast dysfunction during gestational diabetes mellitus (GDM).

METHODS

The study involved forty pregnant women, comprising twenty with GDM and twenty with normal pregnancies. hsa_circ_0003218 expression levels in serum and placental tissues were detected by RT-qPCR. hTR8/ SVneo cells were exposed to high glucose (HG) in vitro and assayed for proliferation, apoptosis, migration, and invasion by CCK-8, flow cytometry, and Transwell tests, respectively. Inflammatory factors were detected by ELISA. TLR4/MyD88/NF-κB cascade and NLRP3 inflammasomes-associated proteins were detected by Western blot.

RESULTS

hsa_circ_0003218 was lowly expressed in placental tissues from GDM patients and HG-treated trophoblasts. hsa_circ_0003218 overexpression lessened HG-induced inhibition of trophoblast proliferation, migration, and invasion, and stimulation of apoptosis and inflammatory factor production. Furthermore, hsa_circ_0003218 prevented the activation of both the TLR4/MyD88/NF-κB cascade and the NLRP3 inflammasome.

CONCLUSIONS

hsa_circ_0003218 improves trophoblast function in GDM by blocking the TLR4/MyD88/NF-κB cascade and preventing NLRP3 inflammasome activation.