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Differentiation-Dependent Changes in Human Trophoblast Expression of Decay-Accelerating Factor Are Modulated by 3′,5′ Cyclic Adenosine Monophosphate

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Abstract

Objective

Decay-accelerating factor (DAF) is a complement regulatory protein that prevents complement-mediated cell lysis. Its expression in human trophoblasts depends on their anatomic location and gestational age. The mechanisms that govern the regulation of its expression in trophoblasts are not understood. The objective of the present study was to investigate the effects of trophoblast differentiation and cyclic adenosine monophosphate (cAMP) on DAF expression.

Methods

Human trophoblasts were isolated from chorionic villi, cultured, and harvested at timed intervals for total RNA extraction and Northern analysis. Expression of DAF was also assessed by immunocytochemistry. In some cultures, the trophoblasts were exposed to the cAMP agonists 8-bromo-cAMP and Sp-cAMPs or the antagonist Rp-cAMPs.

Results

Expression of DAF mRNA increased as the cells differentiated in culture, with the 2.2-kb transcript of membrane-bound DAF appearing first. As differentiation proceeded, the 1.5-kb transcript became the predominant mRNA form. Exposure of the cells to Rp-cAMPs delayed this process; 8-bromo-cAMP accelerated it. Sp-cAMPs selectively up-regulated the 2.2-kb mRNA transcript. Immunocytochemistry confirmed the effects of differentiation on DAF protein expression.

Conclusion

Expression of DAF in human trophoblasts is dependent on the state of cell differentiation, and cAMP is an intracellular modulator of this process. This effect may be mediated through alternative processing of DAF mRNA in its 3′ UT region, which in turn affects mRNA stability.

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Authors and Affiliations

  1. Division of Human Reproduction, Departments of Obstetrics and Gynecology and Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, 3400 Spruce Street, 106 Dulles Building, Philadelphia, Pennsylvania, 19104, USA

    I. K. Zarkadis PhD, A. Omigbodun MD, A. Forson MHS, P. Ziolkiewicz MD, T. Kinoshita PhD, J. D. Lambris PhD & C. Coutifans MD, PhD

  2. Department of Immunoregulation, Osaka University, Japan

    I. K. Zarkadis PhD, A. Omigbodun MD, A. Forson MHS, P. Ziolkiewicz MD, T. Kinoshita PhD, J. D. Lambris PhD & C. Coutifans MD, PhD

Authors
  1. I. K. Zarkadis PhD
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  2. A. Omigbodun MD
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  3. A. Forson MHS
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  4. P. Ziolkiewicz MD
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  5. T. Kinoshita PhD
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  6. J. D. Lambris PhD
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  7. C. Coutifans MD, PhD
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Additional information

Drs. Zarkadis and Omigbodun contributed equally to the work reported in this manuscript.

This study was supported by National Institutes of Health grants HD-30475 (CC), HD-06724 (CC), and AI-30040 (JDL), and by the Rockefeller Foundation.

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Zarkadis, I.K., Omigbodun, A., Forson, A. et al. Differentiation-Dependent Changes in Human Trophoblast Expression of Decay-Accelerating Factor Are Modulated by 3′,5′ Cyclic Adenosine Monophosphate. Reprod. Sci. 4, 47–53 (1997). https://doi.org/10.1016/S1071-5576(96)00061-5

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  • DOI: https://doi.org/10.1016/S1071-5576(96)00061-5

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