Maternal exposure to Di-n-butyl phthalate (DBP) aggravate gestational diabetes mellitus via FoxM1 suppression by pSTAT1 signalling.
The study focused on the toxicological effect of Di-n-butyl phthalate (DBP) on the expression of Phosphorylated signal transducer and activator of transcription 1 (pSTAT1) -regulated Forkhead box protein M1 (FoxM1), which might provide a new understanding of gestational diabetes mellitus (GDM) development and a potential target for treatment. Streptozotocin (STZ) (40 mg/kg) was introduced in maternal rats by intraperitoneal injection on gestation day 0 (GD 0) in the STZ and STZ + DBP groups. DBP was introduced in maternal rats by oral feeding in the STZ + DBP group over the following 3 days (750 mg/kg/day). The changes in fasting blood glucose level in rats were detected on GD 1 and GD 5. The insulin levels in maternal rats and PIBCs were measured on GD 18. The Oral Glucose Tolerance Test (OGTT) test was performed on GD 18 to check the stability of the GDM model. The primary islet β cells (PIBCs) were established for in vitro experiments. We examined the FoxM1 and pSTAT1 expression in pancreas by immunohistochemistry. Real-time PCR and Western blot were used to detect the pSTAR1 and FoxM1 protein and mRNA gene expression levels in PIBCs. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis was used to test the viability and apoptosis of cells. The results showed that the STZ + DBP group had higher glucose and lower insulin secretion levels than the other groups by both fasting test and OGTT. FoxM1 was significantly suppressed while pSTAT1 was highly expressed after DBP exposure. FoxM1 could be regulated by pSTAT1. DBP can influence the progression of GDM through its toxicological effect, which significantly increases the expression of pSTAT1 and suppresses FoxM1, causing a decline in β cell viability.
['Chen|Min|M|', 'Zhao|Sheng|S|', 'Guo|Wen-Huan|WH|', 'Zhu|Yi-Ping|YP|', 'Pan|Lei|L|', 'Xie|Zhi-Wen|ZW|', 'Sun|Wen-Lan|WL|', 'Jiang|Jun-Tao|JT|']
D000818:Animals D002478:Cells, Cultured D003921:Diabetes Mellitus, Experimental D016640:Diabetes, Gestational D003993:Dibutyl Phthalate D052244:Endocrine Disruptors D005260:Female D000072278:Forkhead Box Protein M1 D015870:Gene Expression D006801:Humans D050417:Insulin-Secreting Cells D008297:Male D018811:Maternal Exposure D010766:Phosphorylation D011247:Pregnancy D061251:Primary Cell Culture D051381:Rats D017207:Rats, Sprague-Dawley D050794:STAT1 Transcription Factor D015398:Signal Transduction
Di-n-butyl phthalate Gestational diabetes mellitus FoxM1 pSTAT1 Islet β cells