Abstract
Trophoblast cells play multiple critical roles in pregnancy, notably modulating blastocyst attachment to the endometrium as well as invading into and actively remodeling the endometrium to facilitate biotransport needs of the growing embryo. Despite the importance of trophoblast invasion for processes essential at early stages of pregnancy, much remains unknown regarding the balance of signaling molecules that may influence trophoblast invasion into the endometrium. The goal of this study was to use three-dimensional trophoblast spheroid motility assays to examine the effect of cues from the maternal-fetal interface on trophoblast motility. We report use of a methacrylamide-functionalized gelatin hydrogel to support quantitative analysis of trophoblast outgrowth area and cell viability. We show that this multidimensional model of trophoblast motility can resolve quantifiable differences in outgrowth area and viability in the presence of a known invasion promoter, epidermal growth factor, and a known invasion inhibitor, transforming growth factor β1. We then investigate the sensitivity of trophoblast motility to cortisol, a hormone associated with exogenous stressors. Together, this approach provides a toolset to investigate the coordinated action of physiological and pathophysiological processes on early stages of trophoblast invasion.
| Original language | English |
|---|---|
| Pages (from-to) | 1064-1073 |
| Number of pages | 10 |
| Journal | Tissue Engineering - Part A |
| Volume | 27 |
| Issue number | 15-16 |
| DOIs | |
| State | Published - Aug 1 2021 |
Bibliographical note
Publisher Copyright:© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
Funding
The authors thank Dr. Jee-Wei Emily Chen (U. Illinois) for her incredible mentorship and assistance with method development and Dr. Sara Pedron (U. Illinois) for her assistance with NMR analysis. The authors acknowledge the School of Chemical Sciences Cell Media Facility at the University of Illinois Urbana-Champaign for assistance with cell media and the Core Facilities (Dr. Austin Cyphersmith) at the Institute for Genomic Biology at the University of Illinois Urbana-Champaign for providing assistance with confocal imaging. 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 Urbana-Champaign. Research reported herein was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Numbers R01 DK099528 (B.A.C.H.) 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.).
| Funders | Funder number |
|---|---|
| Department of Chemical and Biomolecular Engineering | |
| National Institutes of Health (NIH) | |
| National Institute of Diabetes and Digestive and Kidney Diseases | R01DK099528 |
| National Institute of Diabetes and Digestive and Kidney Diseases | |
| National Institute of Biomedical Imaging and Bioengineering | R21 EB018481, T32 EB019944 |
| National Institute of Biomedical Imaging and Bioengineering | |
| University of Illinois, Urbana-Champaign |
Keywords
- cortisol
- hydrogel
- maternal-fetal interface
- motility
- three dimensional
- trophoblast
ASJC Scopus subject areas
- Bioengineering
- Biomaterials
- Biochemistry
- Biomedical Engineering