July 21st, 2018

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Oxidative Stress at Low Oxygen Tension Differentially Regulates HERVWE1 and GCM1 Expression in Extravillous Trophoblast Cells
Authors:  Guang-lan Zhang, M.D., Zhi-ming He, M.D., Xiao-mei Shi, M.D., M.S., Chen-yu Gou, M.D., Ph.D., Yu Gao, M.D., and Qun Fang, M.D.
  OBJECTIVE: To analyze HERVWE1, GCM1, and other gene expression by exposure of extravillous cytotrophoblast (TEV) cells to different tensions of oxygen.

STUDY DESIGN: TEV-1 cells were exposed to 20%, 10%, 6%, 3%+6%, and 3% oxygen with and without addition of 50 ng/mL vitamin C for 24 hours. At the end of the experiments, HERVWE1, GCM1, HIF-1α, Nrf-2, human chorionic somatomammotropin, Ki-67, and caspase-3 gene expression were analyzed by quantitative RT-PCR.

RESULTS: We observed a maximal HERVWE1, GCM1, HIF-1α, Nrf-2, and caspase-3 gene expression in the cells after exposure to 10% oxygen. There were no marked changes of these gene expressions in the cells exposed to 3% oxygen. 3% oxygen caused severe hypoxia and oxidative stress to the TEV-1 cells; subsequently, increasing oxygen level up to 6% did not induce significant changes of gene expression. However, addition of vitamin C was able to reverse the oxidative stress effects and significantly upregulate HERVWE1 and GCM1 expression, and potentially promoted TEV-1 differentiation and invasiveness under the extreme hypoxia condition.

CONCLUSION: Therefore, 10% oxygen tension in vitro maximally modulated gene expression, equivalent to the effects under physiological hypoxia in early pregnancy. Vitamin C is a promising adjuvant against oxidative stress under severe hypoxia.
Keywords:  apoptosis, cytotrophoblasts, extravillous cytotrophoblast, hypoxia, invasiveness, proliferation, syncytiotrophoblasts, trophoblasts
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