Abstract

In pregnancy, idiopathic oligohydramnios is an obstetrical complication that compromises maternal health with poor perinatal outcome. Effective therapeutic treatment of this condition has been hampered by the unknown etiology and lack of understanding of cellular and molecular mechanisms that underlie idiopathic oligohydramnios. Amniotic fluid volume (AFV) is determined by intramembranous (IM) transport of amniotic fluid across the amnion and this pathway is regulated to maintain AFV within the normal range. To gain understanding of the causes of idiopathic oligohydramnios, we performed proteomics analysis of the human amnion to investigate the changes in protein expression profiles of cellular transport pathways and regulators in patients with oligohydramnios. Placental amnions from five patients with normal pregnancies and five patients with oligohydramnios were subjected to proteomics experiments followed by bioinformatics analysis. Using Ingenuity Pathway Analysis (IPA) software, five categories of biological functions and multiple canonical pathways within each category were revealed. The top differentially expressed proteins that participate in mediating these pathways were identified. The functional pathways activated include: (a) cellular assembly and organization, (b) cell signaling and energy metabolism, and (c) immunological, infectious, and inflammatory functions. Furthermore, the analysis identified the category of pathways that facilitate molecular endocytosis and vesicular uptake. Under oligohydramniotic conditions, the mediators of clathrin vesicle‐mediated uptake and transport as well as intracellular trafficking mediators were up‐regulated. These findings suggest that idiopathic oligohydramnios may be associated with alternations in cellular organization and immunological functions as well as increases in activity of vesicular transport pathways across the amnion.

Highlights

  • Normal amniotic fluid volume (AFV) is necessary for proper growth and development of the fetus

  • Abnormalities in AFV occur in 7%–10% of ~4 million births in the US annually

  • Proteomics experiments identified a total of 3,476 unique proteins expressed in the human placental amnion of normal and oligohydramniotic patients

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Summary

Introduction

Normal amniotic fluid volume (AFV) is necessary for proper growth and development of the fetus. An excess or deficiency in the volume of this fluid can cause obstetrical problems that compromise maternal and fetal well-being. A majority (>70%) of these cases is diagnosed as oligohydramnios (reduced amniotic fluid volume). Oligohydramnios is associated with poor development of the fetal lung, pulmonary hypoplasia, premature delivery, IUGR (intrauterine growth restriction), umbilical cord compression, and increased risk of cesarean section (Locatelli et al, 2004). Development of oligohydramnios is more prevalent during the third trimester of pregnancy and clinical management of low AFV generally involves ultrasound monitoring and increased maternal fluid intake. Treatment modalities are generally temporary with minimal long-term efficacy largely due to the lack of understanding of the mechanisms that cause the reductions in AFV.

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