Clancy, K. B. H. | Search bioRxiv

bioRxiv2025

Matrix tropism influences endometriotic cell attachment patterns

Due to the extended period for clinical diagnosis, the etiology of endometriotic lesion initiation is not well understood or characterized. Endometriotic lesions are most often found on pelvic tissues and organs, especially the ovaries. To investigate the role of tissue tropism on ovarian endometrioma initiation, we adapted a well-characterized polyacrylamide microarray system to investigate the role of tissue-specific extracellular matrix and adhesion motifs on endometriotic cell attachment, morphology, and size. We report the influence of cell origin (endometriotic vs. non-endometriotic), substrate stiffness mimicking aging and fibrosis, and the role of multicellular (epithelial-stromal) cohorts on cell attachment patterns. We identify multiple ovarian-specific attachment motifs that significantly increase endometriotic (vs. non-endometriotic) cell cohort attachment that could be implicated in early disease etiology.

bioengineering↗

bioRxiv2020

Tuning trophoblast invasion in a gelatin hydrogel via soluble cues from the maternal-fetal interface

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 a three-dimensional trophoblast spheroid invasion assays to examine the effect of cues from the maternal-fetal interface on trophoblast invasion. We report use of a methacrylamide-functionalized gelatin (GelMA) hydrogel to support quantitative analysis of trophoblast outgrowth area and cell viability. We show this multidimensional model of trophoblast invasion 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 {beta}1. We then investigate the sensitivity of trophoblast invasion 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. IMPACT STATEMENTTrophoblast cells from the invading blastocyst play crucial roles in pregnancy, including remodeling endometrial structure to support embryonic biotransport needs; however, much remains unknown regarding the balance of signaling molecules that may influence trophoblast invasion. We show this multidimensional model of invasion can resolve quantifiable differences in outgrowth area and viability in the presence of known invasion promoters and inhibitors and then investigate invasion sensitivity to cortisol, a hormone associated with exogenous stressors. This approach provides a toolset to investigate the coordinated action of molecules from the maternal-fetal interface on trophoblast invasion that may be challenging to study in humans.

bioengineering↗