Abstract: Objective To investigate the regulatory effect of lipocalin-type prostaglandin D2 synthase (L-PGDS) on the inflammation of occurred in placenta of patients with gestational diabetes mellitus (GDM). Methods Clinical data from 150 GDM and 150 normal glucose-tolerant (NG) pregnant women were collected and analyzed. Placental tissues from 30 GDM and 30 NG women were selected, respectively; Placental structure was examined by HE staining microscopy, and L-PGDS mRNA and protein expression were detected using RT-qPCR and Western blot. Human trophoblast cells(HTR-8/SVneo) were divided into eight groups: normal-glucose control(NC), high-glucose(HG,25 mg/L), HG + empty vector(HG+vector), HG + L-PGDS over-expression(HG+OE-L PGDS), HG+empty vector+CAY10471[prostaglandin D2 receptor(DP₂) antagonist](HG+vector+CAY10471), HG + OE-L-PGDS + CAY10471, HG + empty vector + AZD1981 (prostaglandin D2 receptor antagonist)(HG+vector+AZD1981) and HG + OE-L-PGDS + AZD1981. The level of mRNA and protein expression of L-PGDS, TNF-α, and IL-1β was measured by RT-qPCR and Western blot. Results Clinical blood glucose and inflammatory markers were significantly more in the GDM group than in the NG group(P＜0.05). L-PGDS expression in GDM placenta was significantly lower than in NG group (P＜0.05) and was negatively correlated with inflammatory factors. In high glucose-treated cells, L-PGDS expression was down-regulated(P＜0.05), while inflammatory factor expression increased(P＜0.05). Over-expression of L-PGDS reversed the high glucose-induced up-regulation of inflammatory factors, and this anti-inflammatory effect was inhibited by DP2 antagonists. Conclusions High-glucose-induced reduction of L-PGDS is involved in placental inflammatory responses, which is believed to be a potential target for intervention in placental damage in GDM.

Key words: gestational diabetes mellitus, lipocalin-type prostaglandin D₂ synthase, placenta, inflammation, prostaglandin D₂ receptor