Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways
Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322006662 |
| _version_ | 1818518179244146688 |
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| author | Wan-Kun Yan Ying-Nan Liu Shan-Shan Song Jin-Wen Kang Yu Zhang Lei Lu Shu-Wen Wei Qi-Xin Xu Wang-Qing Zhang Xiao-Zheng Liu Yao Wu Ren-Wei Su |
| author_facet | Wan-Kun Yan Ying-Nan Liu Shan-Shan Song Jin-Wen Kang Yu Zhang Lei Lu Shu-Wen Wei Qi-Xin Xu Wang-Qing Zhang Xiao-Zheng Liu Yao Wu Ren-Wei Su |
| author_sort | Wan-Kun Yan |
| collection | DOAJ |
| description | Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced by Fusarium, which acts as estrogen activity because of the similarity of its structure to estrogen. In this study, we used an endometriosis mouse model: 15 days after ovariectomy, endometrial fragments were sutured on the pelvic wall, and exogenous estrogen was supplied using an estrogen-releasing silicone tube embedded subcutaneously. Mice were treated with different doses of ZEA by gavage for 21 days. The results show that ZEA significantly inhibited the growth of ectopic endometrium in a dose-dependent manner. The proliferation of cells decreased while apoptosis increased in the ectopic tissues of ZEA-treated mice compared to the vehicle group. The expression of estrogen receptor-α and its downstream targets MUC1 and p-AKT decreased, indicating an impaired estrogen signaling activity by ZEA treatment. In addition, the decreased expression of pro-inflammatory cytokine Tnf-α, Il-1β, and Il-6, the lower number of macrophages and neutrophils cells, and the inhibited NF-κB signaling pathway suggest the inflammatory response in the ectopic endometrium was also suppressed by ZEA treatment. However, when the exogenous estrogen supply is removed, ZEA, in turn, plays an estrogen-like role that promotes cell proliferation in the ectopic endometrium. In summary, our data suggest ZEA acts as an antagonist in endometriotic tissue when estrogen is sufficient but turns to estrogenic activity in the absence of estrogen in the development of endometriosis. ZEA also inhibits ectopic tissue growth by inhibiting inflammatory response in the endometriosis model. |
| first_indexed | 2024-12-11T01:06:29Z |
| format | Article |
| id | doaj.art-3a7d2847e5ca45da9ad2f114f8409d17 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-11T01:06:29Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-3a7d2847e5ca45da9ad2f114f8409d172022-12-22T01:26:09ZengElsevierEcotoxicology and Environmental Safety0147-65132022-08-01241113826Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathwaysWan-Kun Yan0Ying-Nan Liu1Shan-Shan Song2Jin-Wen Kang3Yu Zhang4Lei Lu5Shu-Wen Wei6Qi-Xin Xu7Wang-Qing Zhang8Xiao-Zheng Liu9Yao Wu10Ren-Wei Su11College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaCorrespondence to: 483 Wushan Road, Guangzhou, Guangdong 510642, China.; College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, ChinaEndometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced by Fusarium, which acts as estrogen activity because of the similarity of its structure to estrogen. In this study, we used an endometriosis mouse model: 15 days after ovariectomy, endometrial fragments were sutured on the pelvic wall, and exogenous estrogen was supplied using an estrogen-releasing silicone tube embedded subcutaneously. Mice were treated with different doses of ZEA by gavage for 21 days. The results show that ZEA significantly inhibited the growth of ectopic endometrium in a dose-dependent manner. The proliferation of cells decreased while apoptosis increased in the ectopic tissues of ZEA-treated mice compared to the vehicle group. The expression of estrogen receptor-α and its downstream targets MUC1 and p-AKT decreased, indicating an impaired estrogen signaling activity by ZEA treatment. In addition, the decreased expression of pro-inflammatory cytokine Tnf-α, Il-1β, and Il-6, the lower number of macrophages and neutrophils cells, and the inhibited NF-κB signaling pathway suggest the inflammatory response in the ectopic endometrium was also suppressed by ZEA treatment. However, when the exogenous estrogen supply is removed, ZEA, in turn, plays an estrogen-like role that promotes cell proliferation in the ectopic endometrium. In summary, our data suggest ZEA acts as an antagonist in endometriotic tissue when estrogen is sufficient but turns to estrogenic activity in the absence of estrogen in the development of endometriosis. ZEA also inhibits ectopic tissue growth by inhibiting inflammatory response in the endometriosis model.http://www.sciencedirect.com/science/article/pii/S0147651322006662EndometriosisZearalenoneEstrogen signalingInflammation |
| spellingShingle | Wan-Kun Yan Ying-Nan Liu Shan-Shan Song Jin-Wen Kang Yu Zhang Lei Lu Shu-Wen Wei Qi-Xin Xu Wang-Qing Zhang Xiao-Zheng Liu Yao Wu Ren-Wei Su Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways Ecotoxicology and Environmental Safety Endometriosis Zearalenone Estrogen signaling Inflammation |
| title | Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways |
| title_full | Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways |
| title_fullStr | Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways |
| title_full_unstemmed | Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways |
| title_short | Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways |
| title_sort | zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways |
| topic | Endometriosis Zearalenone Estrogen signaling Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322006662 |
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