Reduction of Placental Thioredoxin Expression in Diabetic Pregnancies

Abstract

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with its first onset recognized during pregnancy. Patients from GDM are subjected to increase oxidative stress and reduced activity of the placental antioxidant enzymes, all of which contribute to the increase in tissues damages and is associated with adverse perinatal outcome. Thioredoxin (Trx) is a small multifunctional protein ubiquitously expressed in many different tissues. In normal human placenta, it is localized in the trophoblastic region and plays a protective role against oxidative stress in the placenta. Here, a prospective study was carried out in which high-risk women with singleton pregnancies were recruited from the clinic for placental studies. Following delivery, placental specimens were collected and placental protein expression of Trx and TrxR was measured by western blot analysis. A significant reduction of placental Trx and TrxR protein expression was found in diabetic pregnancies in comparison to normal pregnancies. In addition, the reduction of the expression on the two proteins was negatively correlated with the severity of glucose intolerance. In line with the placental Trx protein expression level, we also demonstrated a decrease in placental Trx mRNA expression level in GDM patients, suggesting a possible transcription level down-regulatory mechanism of Trx in GDM patients. Furthermore, using immunohistochemitry techniques, we showed that this reduction of Trx expression was mainly localized in the stromal region of the placental villi. Taking together, we have demonstrated a reduction in placental Trx expression in GDM patients, and further investigation is required to elucidate the role of Trx in GDM placenta.