{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:04:08Z","timestamp":1791615848330,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002641","name":"Konkuk University","doi-asserted-by":"publisher","award":["2020"],"award-info":[{"award-number":["2020"]}],"id":[{"id":"10.13039\/501100002641","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cluster of differentiation 73 (CD73, also known as ecto-5\u2032-nucleotidase) is an enzyme that converts AMP into adenosine. CD73 is a surface enzyme bound to the outside of the plasma membrane expressed in several cells and regulates immunity and inflammation. In particular, it is known to inhibit T cell-mediated immune responses. However, the regulation of CD73 expression by hormones in the uterus is not yet clearly known. In this study, we investigated the expression of CD73 in ovariectomized mice treated with estrogen or progesterone and its regulation in the mouse uterus during the estrous cycle. The level of CD73 expression was dynamically regulated in the uterus during the estrous cycle. CD73 protein expression was high in proestrus, estrus, and diestrus, whereas it was relatively low in the metestrus stage. Immunofluorescence revealed that CD73 was predominantly expressed in the cytoplasm of the luminal and glandular epithelium and the stroma of the endometrium. The expression of CD73 in ovariectomized mice was gradually increased by progesterone treatment. However, estrogen injection did not affect its expression. Moreover, CD73 expression was increased when estrogen and progesterone were co-administered and was inhibited by the pretreatment of the progesterone receptor antagonist RU486. These findings suggest that the expression of CD73 is dynamically regulated by estrogen and progesterone in the uterine environment, and that there may be a synergistic effect of estrogen and progesterone.<\/jats:p>","DOI":"10.3390\/ijms22179403","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T11:01:37Z","timestamp":1630321297000},"page":"9403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Expression and Regulation of CD73 during the Estrous Cycle in Mouse Uterus"],"prefix":"10.3390","volume":"22","author":[{"given":"Jihyun","family":"Lee","sequence":"first","affiliation":[{"name":"Humanized Pig Research Center, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haeun","family":"Park","sequence":"additional","affiliation":[{"name":"Humanized Pig Research Center, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohyeon","family":"Moon","sequence":"additional","affiliation":[{"name":"Humanized Pig Research Center, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-1441","authenticated-orcid":false,"given":"Jeong-Tae","family":"Do","sequence":"additional","affiliation":[{"name":"Humanized Pig Research Center, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwonho","family":"Hong","sequence":"additional","affiliation":[{"name":"Humanized Pig Research Center, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3862-4105","authenticated-orcid":false,"given":"Youngsok","family":"Choi","sequence":"additional","affiliation":[{"name":"Humanized Pig Research Center, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/nrg1225","article-title":"Developmental genetics of the female reproductive tract in mammals","volume":"4","author":"Kobayashi","year":"2003","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.anireprosci.2010.08.030","article-title":"The normal menstrual cycle in women","volume":"124","author":"Mihm","year":"2011","journal-title":"Anim. Reprod. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bertolin, K., and Murphy, B.D. (2014). Reproductive tract changes during the mouse estrous cycle. The Guide to Investigation of Mouse Pregnancy, Elsevier.","DOI":"10.1016\/B978-0-12-394445-0.00007-2"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Byers, S.L., Wiles, M.V., Dunn, S.L., and Taft, R.A. (2012). Mouse estrous cycle identification tool and images. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035538"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Caligioni, C.S. (2009). Assessing reproductive status\/stages in mice. Curr. Protoc. Neurosci., 48.","DOI":"10.1002\/0471142301.nsa04is48"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11154-012-9221-9","article-title":"Endometrial regeneration and endometrial stem\/progenitor cells","volume":"13","author":"Gargett","year":"2012","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s11302-006-9000-8","article-title":"Ecto-5\u2032-nucleotidase: Structure function relationships","volume":"2","year":"2006","journal-title":"Purinergic Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3389\/fphar.2018.00153","article-title":"Unveiling the role of ecto-5\u2032-nucleotidase\/CD73 in astrocyte migration by using pharmacological tools","volume":"9","author":"Adzic","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_9","first-page":"385","article-title":"La nucleotidase et sa reaction avec les desaminations des nucleotides dans le coeur et dans le muscle","volume":"16","author":"Reis","year":"1934","journal-title":"Bull. Soc. Chim. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1042\/bj2850345","article-title":"5\u2032-Nucleotidase: Molecular structure and functional aspects","volume":"285","author":"Zimmermann","year":"1992","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Trapero, C., Vidal, A., Fern\u00e1ndez-Montol\u00ed, M.E., Coroleu, B., Tresserra, F., Barri, P., G\u00f3mez de Aranda, I., S\u00e9vigny, J., Ponce, J., and Matias-Guiu, X. (2019). Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225532"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Choi, H.R., Oh, H.K., Park, S.H., and Jeong, Y.J. (2020). Expression of CD73 is associated with tumor progression and intratumoral inflammation in breast cancer. Asia-Pac. J. Clin. Oncol.","DOI":"10.1111\/ajco.13450"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1093\/annonc\/mdx730","article-title":"Clinical significance of CD73 in triple-negative breast cancer: Multiplex analysis of a phase III clinical trial","volume":"29","author":"Buisseret","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6407","DOI":"10.1158\/0008-5472.CAN-10-1544","article-title":"CD73: A novel target for cancer immunotherapy","volume":"70","author":"Zhang","year":"2010","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"C1079","DOI":"10.1152\/ajpcell.00285.2019","article-title":"Cell type-and tissue-specific functions of ecto-5\u2032-nucleotidase (CD73)","volume":"317","author":"Minor","year":"2019","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11390","DOI":"10.1523\/JNEUROSCI.5817-12.2013","article-title":"Ecto-5\u2032-nucleotidase (CD73)-mediated formation of adenosine is critical for the striatal adenosine A2A receptor functions","volume":"33","author":"Augusto","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kulesskaya, N., V\u00f5ikar, V., Peltola, M., Yegutkin, G.G., Salmi, M., Jalkanen, S., and Rauvala, H. (2013). CD73 is a major regulator of adenosinergic signalling in mouse brain. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066896"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s11302-009-9152-4","article-title":"Ectonucleotidases in the kidney","volume":"5","author":"Shirley","year":"2009","journal-title":"Purinergic Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"F680","DOI":"10.1152\/ajprenal.00312.2014","article-title":"Interactive roles of CD73 and tissue nonspecific alkaline phosphatase in the renal vascular metabolism of 5\u2032-AMP","volume":"307","author":"Jackson","year":"2014","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1083\/jcb.99.1.166","article-title":"Ferritin immunoelectron microscopic localization of 5\u2019-nucleotidase on rat liver cell surface","volume":"99","author":"Matsuura","year":"1984","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1096\/fj.07-100685","article-title":"Ecto-5\u2032-nucleotidase (CD73)-mediated extracellular adenosine production plays a critical role in hepatic fibrosis","volume":"22","author":"Peng","year":"2008","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8127","DOI":"10.4049\/jimmunol.178.12.8127","article-title":"Identification of ectonucleotidases CD39 and CD73 in innate protection during acute lung injury","volume":"178","author":"Eckle","year":"2007","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/pr.2017.176","article-title":"Loss of CD73-mediated extracellular adenosine production exacerbates inflammation and abnormal alveolar development in newborn mice exposed to prolonged hyperoxia","volume":"82","author":"Li","year":"2017","journal-title":"Pediatr. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1161\/CIRCULATIONAHA.106.669697","article-title":"Cardioprotection by ecto-5\u2019-nucleotidase (CD73) and A2B adenosine receptors","volume":"115","author":"Eckle","year":"2007","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s11010-014-2100-9","article-title":"CD73-TNAP crosstalk regulates the hypertrophic response and cardiomyocyte calcification due to \u03b1 1 adrenoceptor activation","volume":"394","author":"Gan","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/nrc3613","article-title":"Immunity, inflammation and cancer: A leading role for adenosine","volume":"13","author":"Antonioli","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1158\/2159-8290.CD-14-0341","article-title":"Targeting cancer-derived adenosine: New therapeutic approaches","volume":"4","author":"Young","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.4049\/jimmunol.1602031","article-title":"Relationship between CD4 regulatory T cells and anergy in vivo","volume":"198","author":"Kalekar","year":"2017","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"813","DOI":"10.3389\/fimmu.2018.00813","article-title":"Controlling the immune suppressor: Transcription factors and microRNAs regulating CD73\/NT5E","volume":"9","author":"Osen","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1172\/JCI128895","article-title":"CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment","volume":"130","author":"Neo","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/ki.2013.43","article-title":"The volatile anesthetic isoflurane induces ecto-5\u2019-nucleotidase (CD73) to protect against renal ischemia and reperfusion injury","volume":"84","author":"Kim","year":"2013","journal-title":"Kidney Int."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Quast, C., Alter, C., Ding, Z., Borg, N., and Schrader, J. (2017). Adenosine Formed by CD73 on T Cells Inhibits Cardiac Inflammation and Fibrosis and Preserves Contractile Function in Transverse Aortic Constriction-Induced Heart Failure. Circ. Heart Fail., 10.","DOI":"10.1161\/CIRCHEARTFAILURE.116.003346"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173667","DOI":"10.1016\/j.ejphar.2020.173667","article-title":"CD73 regulates hepatic stellate cells activation and proliferation through Wnt\/beta-catenin signaling pathway","volume":"890","author":"Jia","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s10815-014-0409-7","article-title":"The role of Wnt signaling members in the uterus and embryo during pre-implantation and implantation","volume":"32","author":"Tepekoy","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s11302-013-9399-7","article-title":"Purinergic signalling in the reproductive system in health and disease","volume":"10","author":"Burnstock","year":"2014","journal-title":"Purinergic Signal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/aja.1001940208","article-title":"Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC-fluorometric detection and spatiotemporal regulation by 5\u2032-nucleotidase and adenosine deaminase","volume":"194","author":"Blackburn","year":"1992","journal-title":"Dev. Dyn."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/j.1440-1681.1998.tb02257.x","article-title":"Evidence for the presence of both P1 and P2 purinoceptors in the rat myometrium","volume":"25","author":"Gillman","year":"1998","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s11302-012-9345-0","article-title":"Ecto-nucleotidases distribution in human cyclic and postmenopausic endometrium","volume":"9","author":"Aliagas","year":"2013","journal-title":"Purinergic Signal."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Texid\u00f3, L., Romero, C., Vidal, A., Garc\u00eda-Valero, J., Fernandez Montoli, M.E., Baixeras, N., Condom, E., Ponce, J., Garc\u00eda-Tejedor, A., and Mart\u00edn-Satu\u00e9, M. (2014). Ecto-nucleotidases activities in the contents of ovarian endometriomas: Potential biomarkers of endometriosis. Mediat. Inflamm., 2014.","DOI":"10.1155\/2014\/120673"},{"key":"ref_40","unstructured":"Gupta, R.C. (2012). Veterinary Toxicology: Basic and Clinical Principles, Academic Press."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mce.2014.07.009","article-title":"The expression of aminoacyl-tRNA-synthetase-interacting multifunctional protein-1 (Aimp1) is regulated by estrogen in the mouse uterus","volume":"399","author":"Jeong","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.mce.2017.02.006","article-title":"Rapid expression of RASD1 is regulated by estrogen receptor-dependent intracellular signaling pathway in the mouse uterus","volume":"446","author":"Kim","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5235","DOI":"10.1210\/endo.139.12.6386","article-title":"Coordination of differential effects of primary estrogen and catecholestrogen on two distinct targets mediates embryo implantation in the mouse","volume":"139","author":"Paria","year":"1998","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1073\/pnas.90.1.55","article-title":"Expression of the epidermal growth factor receptor gene is regulated in mouse blastocysts during delayed implantation","volume":"90","author":"Paria","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9403\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:55:39Z","timestamp":1760165739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,30]]},"references-count":44,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22179403"],"URL":"https:\/\/doi.org\/10.3390\/ijms22179403","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,30]]}}}