{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:15:35Z","timestamp":1784330135360,"version":"3.55.0"},"reference-count":219,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071623"],"award-info":[{"award-number":["82071623"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771553"],"award-info":[{"award-number":["81771553"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871144"],"award-info":[{"award-number":["81871144"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["2017ZZ01016"],"award-info":[{"award-number":["2017ZZ01016"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Shenkang Center for Hospital Development","award":["SHDC2020CR2062B"],"award-info":[{"award-number":["SHDC2020CR2062B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Adenomyosis is a common gynecological disorder traditionally viewed as \u201celusive\u201d. Several excellent review papers have been published fairly recently on its pathogenesis, and several theories have been proposed. However, the falsifiability, explanatory power, and predictivity of these theories are often overlooked. Since adenomyosis can occur spontaneously in rodents and many other species, the animal models may help us unveil the pathogenesis of adenomyosis. This review critically tallies experimentally induced models published so far, with a particular focus on their relevance to epidemiological findings, their possible mechanisms of action, and their explanatory and predictive power. Methods: PubMed was exhaustively searched using the phrase \u201cadenomyosis and animal model\u201d, \u201cadenomyosis and experimental model\u201d, \u201cadenomyosis and mouse\u201d, and \u201cadenomyosis and rat\u201d, and the resultant papers were retrieved, carefully read, and the resultant information distilled. All the retrieved papers were then reviewed in a narrative manner. Results: Among all published animal models of adenomyosis, the mouse model of adenomyosis induced by endometrial\u2013myometrial interface disruption (EMID) seems to satisfy the requirements of falsifiability and has the predictive capability and also Hill\u2019s causality criteria. Other theories only partially satisfy Hill\u2019s criteria of causality. In particular, animal models of adenomyosis induced by hyperestrogenism, hyperprolactinemia, or long-term exposure to progestogens without much epidemiological documentation and adenomyosis is usually not the exclusive uterine pathology consequent to those induction procedures. Regardless, uterine disruption appears to be a necessary but not sufficient condition for causing adenomyosis. Conclusions: EMID is, however, unlikely the sole cause for adenomyosis. Future studies, including animal studies, are warranted to understand how and why in utero and\/or prenatal exposure to elevated levels of estrogen or estrogenic compounds increases the risk of developing adenomyosis in adulthood, to elucidate whether prolactin plays any role in its pathogenesis, and to identify sufficient condition(s) that cause adenomyosis.<\/jats:p>","DOI":"10.3390\/jcm11061744","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T13:24:59Z","timestamp":1647869099000},"page":"1744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Unveiling the Pathogenesis of Adenomyosis through Animal Models"],"prefix":"10.3390","volume":"11","author":[{"given":"Xi","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Benagiano","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, Sapienza, University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xishi","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8511-7624","authenticated-orcid":false,"given":"Sun-Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0002-9378(72)90781-8","article-title":"The elusive adenomyosis of the uterus\u2014Revisited","volume":"112","author":"Bird","year":"1972","journal-title":"Am. 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