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Nutrient restriction and hypoxia independently decrease placental cell proliferation and differentially regulate Igf2, Mtd and Phlda 2 gene expression in vitro
Author(s) -
Bran Patsy M,
Jones Sara
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.544.2
Subject(s) - glut3 , medicine , endocrinology , cell growth , hypoxia (environmental) , messenger rna , placenta , biology , trophoblast , andrology , fetus , chemistry , glut1 , glucose transporter , gene , biochemistry , oxygen , pregnancy , genetics , organic chemistry , insulin
Maternal undernutrition impairs placental and fetal growth resulting in IUGR and developmental programming, but its mechanism and interaction with hypoxia are unknown. Our objectives were to determine the independent and interactive regulation of placental growth by undernutrition and hypoxia and establish a cell culture model of maternal undernutrition. HTR‐8/SVneo human trophoblast cells were cultured in RPMI media and 1.25%–5% FBS with 1–20% oxygen. 75% reduction (NR) of media glucose, essential amino acids, Gln, and vitamins maximally reduced growth. 1% oxygen (Hx) maximally decreased growth and increased Glut3 mRNA 7 fold, whereas 20% oxygen (Nx) maximized growth and minimized Glut 3 mRNA. In a 2×2 factorial experiment at 72 h, both NR and Hx independently reduced growth and Ki67 mRNA levels (p<0.001; 2‐way ANOVA) and increased VEGF and Glut3 mRNA levels (p<0.001). NR independently decreased (p<0.001), but Hx independently increased (p<001), Igf2 mRNA levels. Hx, but not NR, increased Mtd mRNA levels and secreted hCG (p<0.001). NR and Hx only interacted to regulate Phlda2 mRNA such that Hx increased its level in NR, but Nx decreased it (p<0.01). NR and Hx each independently regulated placental cell proliferation, but differentially regulated Igf2, Mtd and Phlda2 mRNA levels, suggesting that each acts in part through common pathways and in part through divergent pathways to regulate placental growth.