Lysosomal Transcription Factor EB (TFEB) in Normal and Gestational Diabetes Mellitus-Complicated Pregnancies

Abstract

Objective: This study aimed to examine the expression of Lysosomal Transcription Factor EB (TFEB), a lysosomal autophagy regulator, in the peripheral blood cells of women with Gestational Diabetes Mellitus (GDM) at delivery) andtheir neonates. Study Design: Single-center, prospective, case-control study of mothers with and without GDM. Maternal and neonatal (umbilical cord) paired blood samples, from term, singleton pregnancies were obtained at delivery. TFEB expresison was evaluated by specific RT-PCR. Results: Forty-three parturients were enrolled; 21 with GDM. Maternal and neonatal characteristics were comparable. Among women with GDM, 16 (76%) had controlled glycemia; 12 (57.1%) with diet alone. TFEB mRNA expression level for mothers with or without GDM and neonates were similar (p=0.776 and p=0.26, respectively). In maternal and neonatal individual paired samples, the mean difference in TFEB mRNA expression levels were wider in the maternalneonatal (venous-umbilical) samples among women with GDM than non-GDM; the major contributor was the higher mean maternal level in this group. Maternal TFEB expression correlated to first trimester maternal BMI (r=0.050), but not with neonatal birth weight. Mean TFEB was higher among female compared to male newborns. Conclusion: The maternal TFEB mRNA expression is determined by early gestational BMI in all women, and later augmented in women with GDM as compared to their new-borns. We hypothesize that an impaired adaptive autophagy response to metabolic stress among women with GDM may play a role in the pathogenesis of GDM and offspring late morbidities.