Zambuto Samantha G, Clancy Kathryn B H, Harley Brendan A C
University of Illinois, Bioengineering, Urbana, Illinois, United States;
University of Illinois, Anthropology, Urbana, Illinois, United States;
Tissue Eng Part A. 2020 Oct 20. doi: 10.1089/ten.SIWH.2020.0097.
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 (GelMA) hydrogel to support quantitative analysis of trophoblast outgrowth area and cell viability. We show 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.
滋养层细胞在妊娠过程中发挥着多种关键作用，尤其在调节囊胚与子宫内膜的附着以及侵入并积极重塑子宫内膜以满足发育中胚胎的生物转运需求方面。尽管滋养层细胞侵入对于妊娠早期至关重要的过程具有重要意义，但关于可能影响滋养层细胞侵入子宫内膜的信号分子平衡，仍有许多未知之处。本研究的目的是使用三维滋养层细胞球体运动分析来研究母胎界面的信号对滋养层细胞运动的影响。我们报告了使用甲基丙烯酰胺功能化明胶（GelMA）水凝胶来支持对滋养层细胞生长面积和细胞活力的定量分析。我们表明，这种滋养层细胞运动的多维模型能够解析在存在已知的侵入促进因子表皮生长因子和已知的侵入抑制因子转化生长因子β1的情况下，生长面积和活力的可量化差异。然后，我们研究了滋养层细胞运动对皮质醇（一种与外源性应激源相关的激素）的敏感性。总之，这种方法提供了一套工具，用于研究生理和病理生理过程对滋养层细胞侵入早期阶段的协同作用。
