Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice
Ovarian endometriosis (OE) provides women of reproductive age with not only severe menstrual pain but also infertility and an increased risk for ovarian carcinogenesis. Whereas peritoneal endometriosis models have been developed with syngeneic implantation of minced uterine tissue and oncogenic K-ra...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231720309319 |
| _version_ | 1818601536025001984 |
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| author | Shotaro Hayashi Tomoko Nakamura Yashiro Motooka Fumiya Ito Li Jiang Shinya Akatsuka Akira Iwase Hiroaki Kajiyama Fumitaka Kikkawa Shinya Toyokuni |
| author_facet | Shotaro Hayashi Tomoko Nakamura Yashiro Motooka Fumiya Ito Li Jiang Shinya Akatsuka Akira Iwase Hiroaki Kajiyama Fumitaka Kikkawa Shinya Toyokuni |
| author_sort | Shotaro Hayashi |
| collection | DOAJ |
| description | Ovarian endometriosis (OE) provides women of reproductive age with not only severe menstrual pain but also infertility and an increased risk for ovarian carcinogenesis. Whereas peritoneal endometriosis models have been developed with syngeneic implantation of minced uterine tissue and oncogenic K-ras allele with conditional Pten deletion within ovarian surface epithelium generated preneoplastic endometrial glandular morphology, followed by endometrioid adenocarcinoma, there has been no mouse model of OE similar to human counterparts, applicable to preclinical studies. Here we for the first time established a murine OE model that reveals infertility, and evaluated the involvement of iron catalyzed oxidative stress in the pathogenesis. Minced uterine tissue from female mice was implanted on ovarian surface of syngeneic mice after bursectomy to induce OE. Ectopic growth of endometrium was observed in association with ovary 4 weeks after implantation in 85.7% (12/14) of the operated mice with our protocol. Endometriotic lesions involved intestine, pancreas and peritoneal wall. Fibrosis around the ovary was prominent and increased time-dependently in the OE group. Iron accumulation was significantly increased in the OE group, leading to oxidative stress in each stage of the follicles as evaluated by 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2′-deoxyguanosine. Expression of follicle stimulating hormone receptor in the follicles revealed a significant decrease during pre-antral, antral and pre-ovulatory phases in the OE group. Finally, the number of pups was significantly reduced in the OE group in comparison to the controls. This model affords an opportunity to evaluate agents or procedures to counteract ovarian endometriosis in the preclinical settings. |
| first_indexed | 2024-12-16T12:52:56Z |
| format | Article |
| id | doaj.art-c48291fa2dfc4457b64bfd7982e9b1be |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-16T12:52:56Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-c48291fa2dfc4457b64bfd7982e9b1be2022-12-21T22:31:06ZengElsevierRedox Biology2213-23172020-10-0137101726Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in miceShotaro Hayashi0Tomoko Nakamura1Yashiro Motooka2Fumiya Ito3Li Jiang4Shinya Akatsuka5Akira Iwase6Hiroaki Kajiyama7Fumitaka Kikkawa8Shinya Toyokuni9Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, Japan; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, JapanDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, JapanDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, JapanDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, JapanDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, JapanDepartment of Obstetrics and Gynecology, Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi, 371-8511, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, JapanDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya, 466-8550, Japan; Center for Low Temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya, 484-8601, Japan; Sydney Medical School, The University of Sydney, NSW, Australia; Corresponding author. Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-Ku, Nagoya 466-8550, Japan.Ovarian endometriosis (OE) provides women of reproductive age with not only severe menstrual pain but also infertility and an increased risk for ovarian carcinogenesis. Whereas peritoneal endometriosis models have been developed with syngeneic implantation of minced uterine tissue and oncogenic K-ras allele with conditional Pten deletion within ovarian surface epithelium generated preneoplastic endometrial glandular morphology, followed by endometrioid adenocarcinoma, there has been no mouse model of OE similar to human counterparts, applicable to preclinical studies. Here we for the first time established a murine OE model that reveals infertility, and evaluated the involvement of iron catalyzed oxidative stress in the pathogenesis. Minced uterine tissue from female mice was implanted on ovarian surface of syngeneic mice after bursectomy to induce OE. Ectopic growth of endometrium was observed in association with ovary 4 weeks after implantation in 85.7% (12/14) of the operated mice with our protocol. Endometriotic lesions involved intestine, pancreas and peritoneal wall. Fibrosis around the ovary was prominent and increased time-dependently in the OE group. Iron accumulation was significantly increased in the OE group, leading to oxidative stress in each stage of the follicles as evaluated by 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2′-deoxyguanosine. Expression of follicle stimulating hormone receptor in the follicles revealed a significant decrease during pre-antral, antral and pre-ovulatory phases in the OE group. Finally, the number of pups was significantly reduced in the OE group in comparison to the controls. This model affords an opportunity to evaluate agents or procedures to counteract ovarian endometriosis in the preclinical settings.http://www.sciencedirect.com/science/article/pii/S2213231720309319Ovarian endometriosisMouse modelIronOxidative stressFollicle stimulating hormone receptorInfertility |
| spellingShingle | Shotaro Hayashi Tomoko Nakamura Yashiro Motooka Fumiya Ito Li Jiang Shinya Akatsuka Akira Iwase Hiroaki Kajiyama Fumitaka Kikkawa Shinya Toyokuni Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice Redox Biology Ovarian endometriosis Mouse model Iron Oxidative stress Follicle stimulating hormone receptor Infertility |
| title | Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice |
| title_full | Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice |
| title_fullStr | Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice |
| title_full_unstemmed | Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice |
| title_short | Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice |
| title_sort | novel ovarian endometriosis model causes infertility via iron mediated oxidative stress in mice |
| topic | Ovarian endometriosis Mouse model Iron Oxidative stress Follicle stimulating hormone receptor Infertility |
| url | http://www.sciencedirect.com/science/article/pii/S2213231720309319 |
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