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Stromal cells, including fibroblasts, are embedded within the connective tissue of the endometrium and contribute to the rapidly changing extracellular matrix (ECM). During the secretory phase, high levels of progesterone induce decidualization of endometrial fibroblasts, which changes their morphology and protein secretion. While it has been shown that the mechanical properties of endometrial tissue, such as the elastic modulus, also contribute to tissue homeostasis and pathology, the interplay between hormones and tissue modulus in contributing to ECM remodeling remains unknown. To address this, we used hydrogels of varying elastic moduli (5 and 15\u2009kPa) to induce decidualization of endometrial fibroblasts. Using metabolic labeling of glycosylated nascent ECM proteins, we then visualized and measured the deposition of newly secreted (nascent) ECM proteins during decidualization. In addition, we designed an automated ImageJ\u2010based workflow for unbiased quantification of nascent ECM deposition. Our results demonstrate that both 5 and 15\u2009kPa hydrogels support decidualization of endometrial stromal fibroblasts as shown by an increase in cell flattening and prolactin secretion. While increased hydrogel modulus alone enhances nascent ECM deposition, decidualization produces an additional increase that converges to similar levels regardless of the initial hydrogel modulus. Collectively, these findings demonstrate that endometrial stromal fibroblasts deposit nascent ECM that is enhanced during decidualization. These observations may provide new insights toward future studies addressing the mechanisms of ECM remodeling in endometrial tissue.<\/jats:p>","DOI":"10.1002\/jbma.70038","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T11:48:48Z","timestamp":1769428128000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanical Cues Regulate Estrogen and Progesterone\u2010Induced Nascent\n                    <scp>ECM<\/scp>\n                    Deposition by Human Endometrial Stromal Fibroblasts"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9195-9307","authenticated-orcid":false,"given":"Grace K.","family":"Hinds","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia USA"},{"name":"Center for Precision Engineering for Health CPE4H University of Pennsylvania  Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arina","family":"Velieva","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia USA"},{"name":"Center for Precision Engineering for Health CPE4H University of Pennsylvania  Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4874-7149","authenticated-orcid":false,"given":"Joshua Yu\u2010Chung","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia USA"},{"name":"Center for Precision Engineering for Health CPE4H University of Pennsylvania  Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1411-5189","authenticated-orcid":false,"given":"Avinava","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia USA"},{"name":"Center for Precision Engineering for Health CPE4H University of Pennsylvania  Philadelphia USA"},{"name":"Department of Materials Science &amp; Engineering University of Michigan  Ann Arbor USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rima","family":"Chavali","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia USA"},{"name":"Center for Precision Engineering for Health CPE4H University of Pennsylvania  Philadelphia USA"},{"name":"Department of Biology University of Pennsylvania  Philadelphia USA"},{"name":"Wharton University of Pennsylvania  Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Loebel","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia USA"},{"name":"Center for Precision Engineering for Health CPE4H University of Pennsylvania  Philadelphia USA"},{"name":"Department of Materials Science &amp; Engineering University of Michigan  Ann Arbor USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719117734319"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41656-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.616893"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00972-2"},{"key":"e_1_2_9_6_1","volume-title":"Endometrial thickness|Radiology Reference Article|Radiopaedia.org","author":"Weerakkody Y.","year":"2010"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-011723-021442"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00221758"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12088"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2018.07.004"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3791\/57684"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","DOI":"10.4081\/ejh.2024.4131","article-title":"The Matrix Stiffness is Increased in the Eutopic Endometrium of Adenomyosis Patients: A Study Based on Atomic Force Microscopy and Histochemistry","volume":"68","author":"Wang X.","year":"2024","journal-title":"European Journal of Histochemistry: EJH"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07697-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2011.09.001"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev333"},{"key":"e_1_2_9_16_1","first-page":"554","article-title":"Organoid Co\u2010Culture Model of the Human Endometrium in a Fully Synthetic Extracellular Matrix Enables the Study of Epithelial\u2010Stromal Crosstalk","volume":"4","author":"Gnecco J. 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