Unveiling the Pathogenesis of Adenomyosis through Animal Models
Background: Adenomyosis is a common gynecological disorder traditionally viewed as “elusive”. 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 th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/6/1744 |
| _version_ | 1797470432075448320 |
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| author | Xi Wang Giuseppe Benagiano Xishi Liu Sun-Wei Guo |
| author_facet | Xi Wang Giuseppe Benagiano Xishi Liu Sun-Wei Guo |
| author_sort | Xi Wang |
| collection | DOAJ |
| description | Background: Adenomyosis is a common gynecological disorder traditionally viewed as “elusive”. 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 “adenomyosis and animal model”, “adenomyosis and experimental model”, “adenomyosis and mouse”, and “adenomyosis and rat”, 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–myometrial interface disruption (EMID) seems to satisfy the requirements of falsifiability and has the predictive capability and also Hill’s causality criteria. Other theories only partially satisfy Hill’s 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. |
| first_indexed | 2024-03-09T19:36:16Z |
| format | Article |
| id | doaj.art-182474345a9e43b1850a3f3aeacae56f |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T19:36:16Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-182474345a9e43b1850a3f3aeacae56f2023-11-24T01:51:52ZengMDPI AGJournal of Clinical Medicine2077-03832022-03-01116174410.3390/jcm11061744Unveiling the Pathogenesis of Adenomyosis through Animal ModelsXi Wang0Giuseppe Benagiano1Xishi Liu2Sun-Wei Guo3Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, ChinaFaculty of Medicine and Dentistry, Sapienza, University of Rome, 00161 Rome, ItalyShanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, ChinaShanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, ChinaBackground: Adenomyosis is a common gynecological disorder traditionally viewed as “elusive”. 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 “adenomyosis and animal model”, “adenomyosis and experimental model”, “adenomyosis and mouse”, and “adenomyosis and rat”, 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–myometrial interface disruption (EMID) seems to satisfy the requirements of falsifiability and has the predictive capability and also Hill’s causality criteria. Other theories only partially satisfy Hill’s 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.https://www.mdpi.com/2077-0383/11/6/1744adenomyosisanimal modelsendometrial–myometrial interface disruptionfalsifiabilitypathogenesispredictivity |
| spellingShingle | Xi Wang Giuseppe Benagiano Xishi Liu Sun-Wei Guo Unveiling the Pathogenesis of Adenomyosis through Animal Models Journal of Clinical Medicine adenomyosis animal models endometrial–myometrial interface disruption falsifiability pathogenesis predictivity |
| title | Unveiling the Pathogenesis of Adenomyosis through Animal Models |
| title_full | Unveiling the Pathogenesis of Adenomyosis through Animal Models |
| title_fullStr | Unveiling the Pathogenesis of Adenomyosis through Animal Models |
| title_full_unstemmed | Unveiling the Pathogenesis of Adenomyosis through Animal Models |
| title_short | Unveiling the Pathogenesis of Adenomyosis through Animal Models |
| title_sort | unveiling the pathogenesis of adenomyosis through animal models |
| topic | adenomyosis animal models endometrial–myometrial interface disruption falsifiability pathogenesis predictivity |
| url | https://www.mdpi.com/2077-0383/11/6/1744 |
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