Extravillous trophoblasts reverse the decidualization induced increase in matrix production by secreting TGFβ antagonists Emilin-1 and Gremlin-1.
Document Type
Article
Publication Date
3-1-2025
Publication Title
Cells Dev
Keywords
JGM, Trophoblasts, Humans, Female, Transforming Growth Factor beta, Decidua, Intercellular Signaling Peptides and Proteins, Pregnancy, Cell Differentiation, Extracellular Matrix, Myofibroblasts, Cell Line, Extravillous Trophoblasts
JAX Source
Cells Dev. 2025;181:203994.
Volume
181
First Page
203994
Last Page
203994
ISSN
2667-2901
PMID
39756583
DOI
https://doi.org/10.1016/j.cdev.2025.203994
Grant
We gratefully acknolwedge the funding provided by the following grant agencies: NICHD (R01HD112424, K99HD105973), NCI (R37CA248161), and AHA (24PRE1196464)
Abstract
The maternal-fetal interface has long been considered as a frontier for an evolutionary arms race due to the close juxtaposition of genetically distinct tissues. In hemochorial species with deep placental invasion, including in humans, maternal stroma prepares its defenses against deep trophoblast invasion by decidualization, a differentiation process characterized by increased stromal cell matrix production, and contractile force generation. Decidualization has evolved from an ancestral wound healing response of fibroblast activation by the endometrial stroma. On the placental side, a new trophoblast cell type in great apes has recently evolved, called extravillous trophoblast (EVT), with an exceptionally high invasive capability. Using HTR8, and differentiated EVTs from trophectodermal stem cells, we show that EVTs partly counter decidual myofibroblast activation derived defenses. This reversal in decidual defenses is achieved by secreted antagonists of Transforming Growth Factor β/Bone morphogenic pathway, specifically Emilin-1 and Gremlin-1. Emilin-1 and Gremlin-1 reverse TGFβ activation in decidual cells, reducing high collagen production, and expression of genes associated with myofibroblast transformation. We also show that these secreted TGFβ antagonists can functionally reverse acquired decidual resistance to trophoblast invasion. As our work highlights new mechanisms evolved by trophoblasts to regulate stromal invasibility, it has broader implications in other invasive processes, including wound healing, and cancer metastasis.
Recommended Citation
Suhail Y,
Liu Y,
Afzal J,
Du W,
Robson P,
Novin A,
Ramasamy R,
Kshitiz .
Extravillous trophoblasts reverse the decidualization induced increase in matrix production by secreting TGFβ antagonists Emilin-1 and Gremlin-1. Cells Dev. 2025;181:203994.