PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy.

Angelo Sirico,Linda Tartaglione,Antonio Lanzone,Giorgia Farì,Sascia Moresi,Vincenzo Arena,Dario Pitocco,Marco Dell’Aquila

doi:10.3390/diagnostics11081356

Abstract

Background: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics. Methods: we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups. Results: PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60′ or 120′ glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60′ or 120′ glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score < 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, p = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, p = 0.05). Conclusion: placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes.

Highlights

Diabetes represents a clinical challenge, especially in pregnant women, where it is crucial to monitor and assess both the maternal and the fetal wellbeing
Background: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics
PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60 or 120 glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60 or 120 glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06)

Summary

Introduction

Diabetes represents a clinical challenge, especially in pregnant women, where it is crucial to monitor and assess both the maternal and the fetal wellbeing. Placentas from women with hyperglycemia are characterized by increased expression of glucose transporters (GLUT) GLUT1 and GLUT3 in the basal syncytiotrophoblast. In these cases, the placenta acts as a regulating glycemic buffer: once within the fetal circulation, glucose is used to cover acute fetal metabolic and energy demands [3]. Maternal hyperglycemia and hyperinsulinemia lead to an increased tissue oxygen consumption, which is responsible for a chronic hypoxemia in the fetoplacental unit and the subsequent upregulation of hormones (erythropoietin, fibroblast growth factor 2, Leptin, insulin-like growth 2) and inflammatory cytokines (interleukin-6, tumor necrosis factor α) that may lead to placental neoangiogenesis and hypervascularization. The aim of the present study was to investigate the expression of PTH-rP and PTH/PTH-rP receptor PTH-R1 in placentas from women with GDM and the relationship between PTH-R1 and PTH-rP expression and the obstetric outcomes

Materials and Methods

Findings

Conclusions