Affiliation:
1. Division of Infectious Diseases Department of Medicine Indiana University School of Medicine 545 Barnhill Dr., EH 305 Indianapolis IN 46202 USA
2. Division of Infectious Diseases Department of Medicine Vanderbilt University Medical Center Nashville TN 37232 USA
3. Division of Infectious Diseases Department of Medicine Department of Microbiology and Immunology University of Louisville Louisville KY 40202 USA
4. Department of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville TN 37232 USA
Abstract
AbstractDuring placental formation, cytotrophoblasts (CTBs) fuse into multinucleate, microvilli‐coated syncytiotrophoblasts (STBs), which contact maternal blood, mediating nutrient, metabolite, and gas exchange between mother and fetus, and providing a barrier against fetal infection. Trophoblasts remodel the surrounding extracellular matrix through the secretion of matrix metalloproteinases (MMPs). Maternal obesity and diabetes mellitus can negatively impact fetal development and may impair trophoblast function. We sought to model the impact of metabolic stress on STB function by examining MMP and hormone secretion. The BeWo CTB cell line was syncytialized to STB‐like cells with forskolin. Cell morphology was examined by electron microscopy and immunofluorescence; phenotype was further assessed by ELISA and RT‐qPCR. STBs were exposed to a metabolic stress cocktail (MetaC: 30 mM glucose, 10 nM insulin, and 0.1 mM palmitic acid). BeWo syncytialization was demonstrated by increased secretion of HCGβ and progesterone, elevated syncytin gene expression (ERVW‐1 and ERVFRD‐1), loss of tight junctions, and increased surface microvilli. MetaC strongly suppressed syncytin gene expression (ERVW‐1 and ERVFRD‐1), suppressed HCGβ and progesterone secretion, and altered both MMP‐9 and MMP‐2 production. Metabolic stress modeling diabetes and obesity altered BeWo STB hormone and MMP production in vitro.
Subject
Organic Chemistry,Molecular Biology,Molecular Medicine,Biochemistry