TY - JOUR
T1 - Effects of Pregnancy-Specific Glycoproteins on Trophoblast Motility in Three-Dimensional Gelatin Hydrogels
AU - Zambuto, Samantha G.
AU - Rattila, Shemona
AU - Dveksler, Gabriela
AU - Harley, Brendan A.C.
N1 - 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. 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. 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. The raw data required to reproduce these findings are available upon request. Please contact the corresponding author to obtain raw data files. Samantha G. Zambuto, Shemona Rattila, Gabriela Dveksler, and Brendan A.C. Harley declare they have no conflict of interest. No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article. This publication has been approved by all co-authors.
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.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Biomaterials
KW - Pregnancy
KW - Proteins
KW - Tissue engineering
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U2 - 10.1007/s12195-021-00715-7
DO - 10.1007/s12195-021-00715-7
M3 - Article
C2 - 35401843
AN - SCOPUS:85123631760
SN - 1865-5025
VL - 15
SP - 175
EP - 191
JO - Cellular and Molecular Bioengineering
JF - Cellular and Molecular Bioengineering
IS - 2
ER -