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The present study exhibited an obvious localization of Egr3 in luminal epithelium and subluminal stroma at implantation sites. Administration of estrogen brought about a distinct gather of Egr3 mRNA in uterine luminal and glandular epithelia. Meanwhile, Egr3 was visualized in the decidua where it might facilitate the proliferation of stromal cells via Ccnd3 and accelerate stromal differentiation, testifying the significance of Egr3 in decidualization. In ovariectomized mice uteri or stromal cells, progesterone advanced the expression of Egr3 whose obstruction counteracted the inducement of stromal differentiation by progesterone. Consistently, Egr3 mediated the influence of cAMP and heparin\u2010binding EGF\u2010like growth factor (HB\u2010EGF) on the differentiation program. Additionally, cAMP\u2010protein kinase A\u00a0(PKA) signaling mediated the adjustment of progesterone on Egr3. Impediment of HB\u2010EGF antagonized the ascendance of Egr3 conferred by cAMP. In stromal cells, Egr3 activated the transcription of Hand2 whose promoter region exhibited the binding enrichment of Egr3. Activation of Hand2 relieved the weakness of stromal differentiation by Egr3 hinderance, whereas knockdown of Hand2 neutralized the guidance of Egr3 overexpression on the differentiation program. Collectively, Egr3 was identified as an important regulator of uterine decidualization through targeting Hand2 in response to progesterone\/cAMP\/HB\u2010EGF pathway.<\/jats:p>","DOI":"10.1002\/cbin.11933","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T08:06:20Z","timestamp":1667289980000},"page":"406-416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Egr3 as an important regulator of uterine decidualization through targeting Hand2"],"prefix":"10.1002","volume":"47","author":[{"given":"Liang","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Medical Center The Second Hospital of Jilin University  Changchun People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai\u2010Fan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Animal Histology and 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