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Hypoxia Up-regulated Angiogenin and Down-regulated Vascular Cell Adhesion Molecule-1 Expression and Secretion in Human Placental Trophoblasts

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Abstract

Objective

Many processes that are involved in cellular invasion, including blastocyst implantation, placental development, and rapidly growing tumors, occur in reduced oxygen environments. It has been surmised that oxygen tension could regulate the cytotrophoblast ability to differentiate and, as a consequence, to express proteins that are critical for placentation. The objective of the current investigation was therefore to test the hypothesis that placental tissues and trophoblast cells in culture, under low oxygen tension, release angiogenic factors that could affect vascular behavior and invasive potential, thus providing a link between abnormal placentation and maternal vascular abnormality.

Methods

Functionally active term placental explant culture and trophoblast cultures were used to demonstrate the secretion profiles of angiogenin and vascular cell adhesion molecule-1 (VCAM-1), and the real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique was employed to demonstrate the mRNA expression under both normoxic and hypoxic conditions.

Results

A significant increase in the secretion (P <.01) and mRNA expression (P <.01) of angiogenin and a significant decrease in the secretion (P <.04) and mRNA expression (P <.03) of VCAM-1 from both term placental explants and trophoblast cultures subjected to hypoxia in vitro were observed.

Conclusion

Because the primary defect in uteroplacental insufficiency is placental maldevelopment probably associated with hypoxia in situ, this study provides molecular evidence to indicate that the differential expression and secretion of angiogenic factors may play an important role in these pathologic conditions.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology and the Department of Paediatrics, National University Hospital, National University of Singapore, Lower Kent Ridge Road, Singapore, 119074

    G. Rajashekhar PhD, A. Loganath PhD, A. C. Roy PhD, S. S. Chong PhD & Y. C. Wong FRCOG

Authors
  1. G. Rajashekhar PhD
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  2. A. Loganath PhD
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  3. A. C. Roy PhD
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  4. S. S. Chong PhD
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  5. Y. C. Wong FRCOG
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Corresponding author

Correspondence to A. Loganath PhD.

Additional information

Supported by generous grants from the National Medical Research Council, Ministry of Health, Singapore (Grant No. NMRC/0467/2000), and the Lee Foundation, Singapore.

The authors express gratitude to Roche Diagnostics, Singapore for their technical support on LightCycler.

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Rajashekhar, G., Loganath, A., Roy, A.C. et al. Hypoxia Up-regulated Angiogenin and Down-regulated Vascular Cell Adhesion Molecule-1 Expression and Secretion in Human Placental Trophoblasts. Reprod. Sci. 12, 310–319 (2005). https://doi.org/10.1016/j.jsgi.2005.02.010

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