Background and purpose: Gestational diabetes mellitus (GDM) is a complication commonly observed in pregnancy, closely associated with increased oxidative stress, inflammatory response, and endoplasmic reticulum (ER) stress. Phoenixin-20 (PNX-20) is a newly reproductive hormone from the hypothalamus that has displayed pleiotropic effects. The promising inhibitory effects of PNX-20 on inflammation have recently been widely reported. The present study aims to investigate the protective effect of PNX-20 on GDM induced placental insults.
Methods: A GDM model was established on C57BLKsJ db/+ mice. The expression level of GPR173 was evaluated using RT-PCR and western blotting analysis. The serum level of glucose, insulin, lipid profiles, and oxidative stress indicators were detected with commercial kits. Fetal analysis was performed to evaluate the reproductive ability. ELISA was used to detect the production of inflammatory factors. The expressions of p-eIF-2α, ATF4, and GRP78 were evaluated with western blotting assay.
Results: Firstly, we found that GPR173 is expressed in the placenta tissue. Secondly, the elevated blood glucose level and lipid level, declined serum insulin level, fetus alive ratio, fetal and placenta weight, and shorten crown-rump length, were observed in the placenta tissue of GDM mice, which were reversed by treatment with PNX-20. Thirdly, the excessively released inflammatory factors and activated oxidative stress in GDM mice were alleviated by the administration of PNX-20. Lastly, the activated eIF-2α/ATF4 ER stress signaling pathway in GDM mice was dramatically suppressed by PNX-20.
Conclusion: Our data revealed a protective property of PNX-20 against placental insults resulted from GDM.
Keywords: ER stress; GPR173; Gestational diabetes mellitus; Inflammatory factors; Phoenixin-20.
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