Altered expression of PGC-1α and PDX1 and their methylation status are associated with fetal glucose metabolism in gestational diabetes mellitus.

PURPOSE: To investigate the effect of gestational diabetes mellitus (GDM) on the expression and methylation of PGC-1α and PDX1 in placenta and their effects on fetal glucose metabolism.

METHODS: 20 cases of full-term placenta without pregnancy complications and umbilical cord abnormalities and 20 cases of GDM group were collected. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery. DNA methylation was quantified at 7 CpG sites within the PGC-1α and PDX1 genes using PCR amplification of bisulfite treated DNA and subsequent DNA sequencing. PGC-1α and PDX1 mRNA levels were measured by reverse transcription-quantitative PCR (RT-qPCR). Meanwhile, the placental insulin, blood glucose and HbA1c levels were determined.

RESULTS: The fetus birth weight and placental weight in GDM group were significantly higher than those in control group (P < 0.05). Insulin, HbA1c and blood glucose levels in GDM group were significantly higher than those in control group (P < 0.01). Insulin content was positively correlated with newborn birth weight and placental weight while HbA1c and blood glucose were positively correlated with insulin concentration (r = 0.92, P < 0.01, r = 0.85, P < 0.01). The levels of PGC-1α and PDX1 mRNA were lower in the GDM group compared to the control group. The methylation level of PGC-1α gene was higher in the GDM group compared to the control group (P < 0.05). Blood glucose was negatively correlated with the expression of PGC-1α and PDX1 mRNA in the placenta (r = -0.42, P < 0.01, r = -0.49, P < 0.01).

CONCLUSION: The changes of epigenetic modification of PGC-1α gene in pregnant women with gestational diabetes mellitus may be a mechanism of abnormal glucose metabolism in offspring.