Circulating Interleukin-6 Mediates PM2.5-Induced Ovarian Injury by Suppressing the PPARγ Pathway
Exposure to airborne fine particulate matter (PM2.5) is strongly associated with poor fertility and ovarian damage. However, the mechanism underlying this remains largely unclear. Here, we found that PM2.5 markedly impaired murine ovarian reserve, decreased hormone levels, and aggravated ovarian inf...
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| Language: | English |
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American Association for the Advancement of Science (AAAS)
2024-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0538 |
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| author | Yingying Chen Jinjin Zhang Tianyu Zhang Yaling Wu Yueyue Xi Tong Wu Mo Li Yan Li Su Zhou Mingfu Wu Shixuan Wang |
| author_facet | Yingying Chen Jinjin Zhang Tianyu Zhang Yaling Wu Yueyue Xi Tong Wu Mo Li Yan Li Su Zhou Mingfu Wu Shixuan Wang |
| author_sort | Yingying Chen |
| collection | DOAJ |
| description | Exposure to airborne fine particulate matter (PM2.5) is strongly associated with poor fertility and ovarian damage. However, the mechanism underlying this remains largely unclear. Here, we found that PM2.5 markedly impaired murine ovarian reserve, decreased hormone levels, and aggravated ovarian inflammation. Circulating interleukin-6 (IL-6) was elevated in PM2.5-exposed mice and was further confirmed to mediate this damage by IL-6 recombinant protein intervention. PM2.5 exposure led to increased alveolar macrophage infiltration in the lungs. However, alveolar macrophage clearance with clodronate liposomes could not fully reverse the elevated IL-6 levels and ovarian injury, suggesting that alveolar macrophages were probably not the only source of circulating IL-6. Further experiments indicated that IL-6 mainly targeted ovarian theca–interstitial cells and impaired testosterone synthesis via suppressing the peroxisome proliferator-activated receptor γ (PPARγ) pathway. In addition, apoptosis of granulosa cells and restriction of follicular growth were observed in co-cultures with IL-6-treated theca–interstitial cells, which could be further reversed by the PPARγ agonist. Moreover, IL-6-neutralizing antibodies ameliorated PM2.5-induced ovarian damage. Notably, increased levels of circulating IL-6 were observed in premature ovarian aging patients and were inversely associated with their ovarian function. In summary, our findings offer a mechanistic explanation for PM2.5-induced ovarian dysfunction and verify IL-6 as a biomarker and potential therapeutic target. |
| format | Article |
| id | doaj-art-b372ec66befa4254bfd09afbcabaa35b |
| institution | OA Journals |
| issn | 2639-5274 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
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| series | Research |
| spelling | doaj-art-b372ec66befa4254bfd09afbcabaa35b2025-08-20T02:30:45ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742024-01-01710.34133/research.0538Circulating Interleukin-6 Mediates PM2.5-Induced Ovarian Injury by Suppressing the PPARγ PathwayYingying Chen0Jinjin Zhang1Tianyu Zhang2Yaling Wu3Yueyue Xi4Tong Wu5Mo Li6Yan Li7Su Zhou8Mingfu Wu9Shixuan Wang10Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Exposure to airborne fine particulate matter (PM2.5) is strongly associated with poor fertility and ovarian damage. However, the mechanism underlying this remains largely unclear. Here, we found that PM2.5 markedly impaired murine ovarian reserve, decreased hormone levels, and aggravated ovarian inflammation. Circulating interleukin-6 (IL-6) was elevated in PM2.5-exposed mice and was further confirmed to mediate this damage by IL-6 recombinant protein intervention. PM2.5 exposure led to increased alveolar macrophage infiltration in the lungs. However, alveolar macrophage clearance with clodronate liposomes could not fully reverse the elevated IL-6 levels and ovarian injury, suggesting that alveolar macrophages were probably not the only source of circulating IL-6. Further experiments indicated that IL-6 mainly targeted ovarian theca–interstitial cells and impaired testosterone synthesis via suppressing the peroxisome proliferator-activated receptor γ (PPARγ) pathway. In addition, apoptosis of granulosa cells and restriction of follicular growth were observed in co-cultures with IL-6-treated theca–interstitial cells, which could be further reversed by the PPARγ agonist. Moreover, IL-6-neutralizing antibodies ameliorated PM2.5-induced ovarian damage. Notably, increased levels of circulating IL-6 were observed in premature ovarian aging patients and were inversely associated with their ovarian function. In summary, our findings offer a mechanistic explanation for PM2.5-induced ovarian dysfunction and verify IL-6 as a biomarker and potential therapeutic target.https://spj.science.org/doi/10.34133/research.0538 |
| spellingShingle | Yingying Chen Jinjin Zhang Tianyu Zhang Yaling Wu Yueyue Xi Tong Wu Mo Li Yan Li Su Zhou Mingfu Wu Shixuan Wang Circulating Interleukin-6 Mediates PM2.5-Induced Ovarian Injury by Suppressing the PPARγ Pathway Research |
| title | Circulating Interleukin-6 Mediates PM2.5-Induced Ovarian Injury by Suppressing the PPARγ Pathway |
| title_full | Circulating Interleukin-6 Mediates PM2.5-Induced Ovarian Injury by Suppressing the PPARγ Pathway |
| title_fullStr | Circulating Interleukin-6 Mediates PM2.5-Induced Ovarian Injury by Suppressing the PPARγ Pathway |
| title_full_unstemmed | Circulating Interleukin-6 Mediates PM2.5-Induced Ovarian Injury by Suppressing the PPARγ Pathway |
| title_short | Circulating Interleukin-6 Mediates PM2.5-Induced Ovarian Injury by Suppressing the PPARγ Pathway |
| title_sort | circulating interleukin 6 mediates pm2 5 induced ovarian injury by suppressing the pparγ pathway |
| url | https://spj.science.org/doi/10.34133/research.0538 |
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