Background and Aims
Pre-existing maternal obesity and Gestational diabetes mellitus (GDM) are two significant pregnancy complications. They lead to increased fetal adiposity which is associated with many adverse metabolic disturbances in the offspring. It is postulated that increased placental transport of nutrients such as glucose, fatty acids, and amino acids is one of the mechanisms responsible for metabolic disorders. While previous studies show increased placental expression of glucose and fatty acid transporters complicated by maternal obesity and/or GDM, there is a paucity of data on amino acid transporters. Thus, the aim of this study was to determine the mRNA expression of amino acid transporters in placentae from obese\non-obese women with GDM compared with BMI-matched uncomplicated pregnancies.
Methods
Placental mRNA expression of amino acid transporters was investigated in human placentae obtained from women with diet-managed GDM (n=22 non-obese and 12 obese), insulin-controlled GDM (n=19 non-obese and 16 obese) and BMI matched normal glucose tolerance (NGT) (n=18 non-obese and 15 obese). The mRNA expression of hCAT1, hCAT2, SNAT1, LAT1, NTRK2, 4F2hc, SLC6A4, SLC6A9, SLC6A12, and SLC6A2 was determined using a Fluidigm Biomark™ HD system. Data was analysed using the average of three housekeeping genes (18S rRNA, YWHAZ, and TBP) and relative quantification was performed according to the 2-ΔΔCT method. Statistical difference was performed using Mann-Whitney test and p <0.05 was considered significant.
Results
SNAT1, hCAT2, and NTRK2 showed significantly increased mRNA relative to the three housekeeping genes. Specifically, placental SNAT1 and hCAT2 mRNA was significantly increased in diet-managed GDM non-obese and obese compared with BMI-matched NGT women. Placental NTRK2 mRNA was also significantly increased in obese women with insulin-controlled GDM when compared with BMI-matched NGT women. However, there was no significant difference in the placental mRNA expression was observed for any of amino acid transporters in NGT non-obese compared with NGT obese women.
Conclusion
This study reports that GDM-affected pregnancies (non-obese\obese) are associated with an increase in placental mRNA expression of SNAT1, hCAT2, and NTRK2 amino acid transporters. In these pregnancies increased supply of amino acids may lead to fetal overgrowth possibly via neoglucogenesis pathway. However, the placental protein expressions of SNAT1, hCAT2, and NTRK2 in GDM, obese, and non-obese pregnancies warrant further investigations.