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Effects of Pregnancy-Specific Glycoproteins on Trophoblast Motility in Three-Dimensional Gelatin Hydrogels

Cellular and Molecular Bioengineering volume 15, pages 175–191 (2022)Cite this article

Abstract

Introduction

Trophoblast invasion is a complex biological process necessary for establishment of pregnancy; however, much remains unknown regarding what signaling factors coordinate the extent of invasion. Pregnancy-specific glycoproteins (PSGs) are some of the most abundant circulating trophoblastic proteins in maternal blood during human pregnancy, with maternal serum concentrations rising to as high as 200–400 μg/mL at term.

Methods

Here, we employ three-dimensional (3D) trophoblast motility assays consisting of trophoblast spheroids encapsulated in 3D gelatin hydrogels to quantify trophoblast outgrowth area, viability, and cytotoxicity in the presence of PSG1 and PSG9 as well as epidermal growth factor and Nodal.

Results

We show PSG9 reduces trophoblast motility whereas PSG1 increases motility. Further, we assess bulk nascent protein production by encapsulated spheroids to highlight the potential of this approach to assess trophoblast response (motility, remodeling) to soluble factors and extracellular matrix cues.

Conclusions

Such models provide an important platform to develop a deeper understanding of early pregnancy.

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Acknowledgments

The authors thank Dr. Gil Mor (Yale University School of Medicine, New Haven, CT) for providing the Swan71 cells. The authors also thank the School of Chemical Sciences Cell Media Facility (Dr. Sandy McMasters) at the University of Illinois at Urbana-Champaign for assistance with cell media for the nascent protein experiment and the Institute for Genomic Biology Core Facilities (Dr. Austin Cyphersmith) at the University of Illinois at Urbana-Champaign for assistance with confocal imaging.

Author Contributions

SGZ designed and conducted experiments, analyzed resultant data, and wrote the manuscript. SR generated the recombinant PSGs. GD conceived of the study and edited the manuscript. BACH conceived of the study, designed experiments, provided guidance, and edited the manuscript.

Funding

Research reported was supported by the National Institutes of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Numbers R01 DK0099528 (B.A.C.H.), National Institute of Allergy and Infectious Diseases under Award R21 AI1290918 (G.D.) and by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Numbers R21 EB018481 (B.A.C.H.) and T32 EB019944 (S.G.Z.). The content herein is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Defense. The authors also gratefully acknowledge additional funding provided by the Department of Chemical & Biomolecular Engineering and the Carl R. Woese Institute for Genomic Biology at the University of Illinois at Urbana-Champaign.

Data Availability

The raw data required to reproduce these findings are available upon request. Please contact the corresponding author to obtain raw data files.

Conflict of interest

Samantha G. Zambuto, Shemona Rattila, Gabriela Dveksler, and Brendan A.C. Harley declare they have no conflict of interest.

Ethical Approval

No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Samantha G. Zambuto

  2. Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD, 20814, USA

    Shemona Rattila & Gabriela Dveksler

  3. Department Chemical and Biomolecular Engineering, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 110 Roger Adams Laboratory, 600 S. Mathews Ave, Urbana, IL, 61801, USA

    Brendan A. C. Harley

  4. Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Brendan A. C. Harley

Authors
  1. Samantha G. Zambuto
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  2. Shemona Rattila
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  3. Gabriela Dveksler
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  4. Brendan A. C. Harley
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Correspondence to Brendan A. C. Harley.

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Zambuto, S.G., Rattila, S., Dveksler, G. et al. Effects of Pregnancy-Specific Glycoproteins on Trophoblast Motility in Three-Dimensional Gelatin Hydrogels. Cel. Mol. Bioeng. 15, 175–191 (2022). https://doi.org/10.1007/s12195-021-00715-7

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Keywords

  • Biomaterials
  • Tissue engineering
  • Pregnancy
  • Proteins