{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:38:02Z","timestamp":1786325882449,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T00:00:00Z","timestamp":1671840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2019A1515010954"],"award-info":[{"award-number":["2019A1515010954"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2021A1515012089"],"award-info":[{"award-number":["2021A1515012089"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During decidualization in rodents, uterine stromal cells undergo extensive reprogramming to differentiate into distinct cell types, forming primary decidual zones (PDZs), secondary decidual zones (SDZs), and layers of undifferentiated stromal cells. The formation of secondary decidual zones is accompanied by extensive angiogenesis. During early pregnancy, besides ovarian estrogen, de novo synthesis of estrogen in the uterus is essential for the progress of decidualization. However, the molecular mechanisms are not fully understood. Studies have shown that Cystatin B (Cstb) is highly expressed in the decidual tissue of the uterus, but the regulation and mechanism of Cstb in the process of decidualization have not been reported. Our results showed that Cstb was highly expressed in mouse decidua and artificially induced deciduoma via in situ hybridization and immunofluorescence. Estrogen stimulates the expression of Cstb through the Estrogen receptor (ER)\u03b1. Moreover, in situ synthesis of estrogen in the uterus during decidualization regulates the expression of Cstb. Silencing the expression of Cstb affects the migration ability of stromal cells. Knockdown Cstb by siRNA significantly inhibits the expression of Dtprp, a marker for mouse decidualization. Our study identifies a novel estrogen target, Cstb, during decidualization and reveals that Cstb may play a pivotal role in angiogenesis during mouse decidualization via the Angptl7.<\/jats:p>","DOI":"10.3390\/ijms24010302","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:40:39Z","timestamp":1672116039000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Expression and Regulation of a Novel Decidual Cells-Derived Estrogen Target during Decidualization"],"prefix":"10.3390","volume":"24","author":[{"given":"Lin","family":"Lu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingni","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-9947","authenticated-orcid":false,"given":"Zhenshan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijin","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songqi","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohuan","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrg1808","article-title":"Roadmap to embryo implantation: Clues from mouse models","volume":"7","author":"Wang","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1210\/er.2003-0020","article-title":"Molecular cues to implantation","volume":"25","author":"Dey","year":"2004","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/bs.ctdb.2016.12.005","article-title":"Estrogen Hormone Biology","volume":"125","author":"Hamilton","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23534","DOI":"10.1074\/jbc.M114.588897","article-title":"Egr1 protein acts downstream of estrogen-leukemia inhibitory factor (LIF)-STAT3 pathway and plays a role during implantation through targeting Wnt4","volume":"289","author":"Liang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_5","first-page":"342","article-title":"Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis","volume":"15","author":"Simpson","year":"1994","journal-title":"Endocr. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12542","DOI":"10.1073\/pnas.0901647106","article-title":"De novo synthesis of estrogen in pregnant uterus is critical for stromal decidualization and angiogenesis","volume":"106","author":"Das","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-13489-4","article-title":"Primary decidual zone formation requires Scribble for pregnancy success in mice","volume":"10","author":"Yuan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0272-6386(87)80126-9","article-title":"Control of vascular reactivity in pregnancy","volume":"9","author":"Gant","year":"1987","journal-title":"Am. J. Kidney Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1016\/S0301-2115(03)00173-8","article-title":"Uterine blood flow--a determinant of fetal growth","volume":"110","author":"Lang","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1002\/emmm.201302618","article-title":"VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy","volume":"5","author":"Kim","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1530\/REP-09-0147","article-title":"Regulation of endometrial vascular remodelling: Role of the vascular endothelial growth factor family and the angiopoietin-TIE signalling system","volume":"138","author":"Girling","year":"2009","journal-title":"Reproduction"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S1726-4901(09)70052-8","article-title":"Roles of estrogen and progesterone in endometrial hemodynamics and vascular endothelial growth factor production","volume":"72","author":"Wen","year":"2009","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1038\/onc.2013.314","article-title":"Stefin B deficiency reduces tumor growth via sensitization of tumor cells to oxidative stress in a breast cancer model","volume":"33","author":"Butinar","year":"2014","journal-title":"Oncogene"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.bbcan.2018.09.002","article-title":"Dynamic matrisome: ECM remodeling factors licensing cancer progression and metastasis","volume":"1870","author":"Yuzhalin","year":"2018","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.biochi.2019.05.002","article-title":"Cystatins in cancer progression: More than just cathepsin inhibitors","volume":"166","author":"Breznik","year":"2019","journal-title":"Biochimie"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1158\/0008-5472.CAN-19-2578","article-title":"Cancer cell-derived matrisome proteins promote metastasis in pancreatic ductal adenocarcinoma","volume":"80","author":"Tian","year":"2020","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1095\/biolreprod.115.129296","article-title":"\u2018Conceptualizing\u2019 the endometrium: Identification of conceptus-derived proteins during early pregnancy in cattle","volume":"92","author":"Forde","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1093\/molehr\/gah172","article-title":"Role of cathepsins and cystatins in patients with recurrent miscarriage","volume":"11","author":"Nakanishi","year":"2005","journal-title":"Mol. Hum. Reprod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1152\/physrev.00024.2016","article-title":"Membrane and nuclear estrogen receptor alpha actions: From tissue specificity to medical implications","volume":"97","author":"Arnal","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.mce.2011.07.027","article-title":"The regulation of embryo implantation and endometrial decidualization by progesterone receptor signaling","volume":"358","author":"Large","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.7150\/ijbs.45586","article-title":"Collagen at the maternal-fetal interface in human pregnancy","volume":"16","author":"Shi","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1002\/1873-3468.12645","article-title":"Molecular characterization of lysyl oxidase-mediated extracellular matrix remodeling during mouse decidualization","volume":"591","author":"Li","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/humupd\/dmw004","article-title":"The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding","volume":"22","author":"Schatz","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1093\/humrep\/dez139","article-title":"Tissue stiffness at the human maternal-fetal interface","volume":"34","author":"Abbas","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1053\/plac.2001.0748","article-title":"Differential activity of cathepsin L in human placenta at two different stages of gestation","volume":"23","author":"Divya","year":"2002","journal-title":"Placenta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1530\/REP-09-0381","article-title":"The embryo\u2019s cystatin C and F expression functions as a protective mechanism against the maternal proteinase cathepsin S in mice","volume":"139","author":"Schanz","year":"2010","journal-title":"Reproduction"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhang, C., Yang, H., Pan, L., Zhao, G., Zhang, R., Zhang, T., Xiao, Z., Tong, Y., Zhang, Y., and Hu, R. (2021). Hepatitis B virus x protein (HBx) suppresses transcription factor EB (TFEB) resulting in stabilization of integrin beta 1 (ITGB1) in hepatocellular carcinoma cells. Cancers, 13.","DOI":"10.3390\/cancers13051181"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2152\/jmi.52.1","article-title":"Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells","volume":"52","author":"Nomura","year":"2005","journal-title":"J. Med. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16189","DOI":"10.1073\/pnas.0806219105","article-title":"Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migration","volume":"105","author":"Grewal","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10815-017-1107-z","article-title":"High-quality human preimplantation embryos actively influence endometrial stromal cell migration","volume":"35","author":"Berkhout","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1210\/en.2008-1207","article-title":"Vascular endothelial growth factor receptor 2 (VEGFR-2) functions to promote uterine decidual angiogenesis during early pregnancy in the mouse","volume":"150","author":"Douglas","year":"2009","journal-title":"Endocrinology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.7150\/ijms.38219","article-title":"Investigating novel genes potentially involved in endometrial adenocarcinoma using next-generation sequencing and bioinformatic approaches","volume":"16","author":"Tang","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Toyono, T., Usui, T., Yokoo, S., Taketani, Y., Nakagawa, S., Kuroda, M., Yamagami, S., and Amano, S. (2015). Angiopoietin-like 7 is an anti-angiogenic protein required to prevent vascularization of the cornea. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116838"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s10456-014-9435-4","article-title":"Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer","volume":"17","author":"Parri","year":"2014","journal-title":"Angiogenesis"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Song, Z., Li, B., Li, M., Luo, J., Hong, Y., He, Y., Chen, S., Yang, Z., Liang, C., and Yang, Z. (2022). Caveolin-1 Regulation and Function in Mouse Uterus during Early Pregnancy and under Human In Vitro Decidualization. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073699"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.1681\/ASN.V11suppl_2s101","article-title":"Effect of the genetic background on the phenotype of mouse mutations","volume":"11","author":"Montagutelli","year":"2000","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1101\/gr.6.10.986","article-title":"Real time quantitative PCR","volume":"6","author":"Heid","year":"1996","journal-title":"Genome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1095\/biolreprod67.1.351","article-title":"Differential expression of microsomal prostaglandin e synthase at implantation sites and in decidual cells of mouse uterus","volume":"67","author":"Ni","year":"2002","journal-title":"Biol. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23473","DOI":"10.1074\/jbc.M800406200","article-title":"MicroRNA expression and regulation in mouse uterus during embryo implantation","volume":"283","author":"Hu","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1354\/vp.42-4-405","article-title":"Technical aspects of immunohistochemistry","volume":"42","year":"2005","journal-title":"Vet. Pathol."},{"key":"ref_41","first-page":"e4","article-title":"Immunofluorescence techniques","volume":"133","author":"Odell","year":"2013","journal-title":"J. Investig. Derm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:50:14Z","timestamp":1760147414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,24]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010302"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010302","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,24]]}}}