Zambuto Samantha G, Rattila Shemona, Dveksler Gabriela, Harley Brendan A C
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 USA.
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814 USA.
Cell Mol Bioeng. 2022 Jan 27;15(2):175-191. doi: 10.1007/s12195-021-00715-7. eCollection 2022 Apr.
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.
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.
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.
Such models provide an important platform to develop a deeper understanding of early pregnancy.
滋养层细胞侵袭是建立妊娠所必需的复杂生物学过程；然而，关于哪些信号因子协调侵袭程度仍有许多未知之处。妊娠特异性糖蛋白（PSG）是人类妊娠期间母体血液中最丰富的循环滋养层蛋白之一，足月时母体血清浓度可高达200 - 400μg/mL。
在此，我们采用三维（3D）滋养层细胞运动分析，该分析由包裹在3D明胶水凝胶中的滋养层球体组成，以量化在PSG1和PSG9以及表皮生长因子和Nodal存在下滋养层细胞的生长面积、活力和细胞毒性。
我们发现PSG9降低滋养层细胞运动性，而PSG1增加运动性。此外，我们评估包裹球体的新生蛋白总产量，以突出这种方法评估滋养层细胞对可溶性因子和细胞外基质信号的反应（运动性、重塑）的潜力。
此类模型为更深入了解早期妊娠提供了重要平台。
