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Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes

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Abstract

Background

Many parallels exist between growth and development of the placenta and that of cancer. One parallel is shared expression of antigens that may have functional importance and may be recognized by the immune system. Here, we characterize expression and regulation of one such antigen, Trophoblast glycoprotein (TPGB; also called 5T4), in the placenta across gestation, in placentas of preeclamptic (PE) pregnancies, and in purified microvesicles and exosomes.

Methods

Trophoblast glycoprotein expression was analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immuno-histochemistry. Regulation of 5T4 in cytotrophoblast cells was examined under either differentiating conditions of epidermal growth factor or under varying oxygen conditions. Microvesicles and exosomes were purified from supernatant of cultured and perfused placentas.

Results

Trophoblast glycoprotein expression was prominent at the microvillus surface of syncytio-trophoblast and on the extravillous trophoblast cells, with minimal expression in undifferentiated cytotrophoblasts and normal tissues. Trophoblast glycoprotein expression was elevated in malignant tumors. In cytotrophoblasts, 5T4 was induced by in vitro differentiation, and its messenger RNA (mRNA) was increased under conditions of low oxygen. PE placentas expressed higher 5T4 mRNA than matched control placentas. Trophoblast glycoprotein was prominent within shed placental microvesicles and exosomes.

Conclusion

Given the potential functional and known immunological importance of 5T4 in cancer, these studies reveal a class of proteins that may influence placental development and/or sensitize the maternal immune system. In extravillous trophoblasts, 5T4 may function in epithelial-to-mesenchymal transition during placentation. The role of syncytiotrophoblast 5T4 is unknown, but its abundance in shed syncytial vesicles may signify route of sensitization of the maternal immune system.

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Author information

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA

    S. M. K. Alam PhD, S. Jasti PhD & M. G. Petroff PhD

  2. Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

    S. M. K. Alam PhD

  3. Department of Pathobiology and Diagnostic Investigation, Michigan State University, 474 S. Shaw Lane, East Lansing, MI, USA

    S. K. Kshirsagar MS, B. K. Petroff DVM, PhD & M. G. Petroff PhD

  4. Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK

    D. S. Tannetta PhD, R. A. Dragovic PhD, C. W. Redman MD & I. L. Sargent PhD

  5. Center for Women’s Health, Overland Park, KS, USA

    H. C. Hodes MD & T. L. Nauser MD

  6. Sparrow Hospital, Lansing, MI, USA

    T. Fortes MD, A. M. Filler DO & D. R. Martin DO

  7. College of Human Medicine, Michigan State University, East Lansing, MI, USA

    T. Fortes MD, A. M. Filler DO & K. Behan

  8. Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA

    T. A. Fields MD, PhD

  9. Veterinary Diagnostic Laboratory, Michigan State University, East Lansing, MI, USA

    B. K. Petroff DVM, PhD

  10. Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA

    M. G. Petroff PhD

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  1. S. M. K. Alam PhD
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  2. S. Jasti PhD
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Correspondence to M. G. Petroff PhD.

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Alam, S.M.K., Jasti, S., Kshirsagar, S.K. et al. Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes. Reprod. Sci. 25, 185–197 (2018). https://doi.org/10.1177/1933719117707053

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