(640) O-GlcNAc transferase contributes to sex-specific placental deregulation in gestational diabetes

OGT expression was significantly reduced in male placentas collected from mothers with GDM but was not reduced in female placentas. Simulated tissue culture model of knockdown OGT (siOGT) identified 68 genes with significant deregulated expression ( >2-fold change and adjusted p < 0.05). Furthermore, siOGT transcriptome had a 32% overlap with known GDM-related genes and 21% overlap with that of preeclampsia. Notably, placenta-growth hormone (GH) production was significantly elevated while compensatory factors against GH-related insulin resistance, such as Leptin, were diminished. Inflammatory and immunologic factors with known toxic effect on β cell mass were also increased, altogether representing a decompensatory diabetic profile.

Conclusion:

We demonstrated that O-GlcNAcylation deregulation in OGT level contributes to improper placental hormone production, which would disturb gestational metabolic homeostasis. In addition to building on new fundamental knowledge in placental pathophysiology, this project opens new avenues for prognostic and treatment considerations in GDM pregnancies.