Synergistic effects of PS-NPs and Cd on ovarian toxicity in adolescent rats: Ferroptosis by induction of mitochondrial redox imbalance via the SIRT3-SOD2/Gpx4 pathway
Nanoplastics (NPs) are an emerging class of pollutants. They can act as a“Trojan horse” to change the bioavailability and toxicity of heavy metals in the environment. However, research on the combined toxicity of heavy metals and NPs is scarce, especially during the critical developmental period of...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324016981 |
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| author | Hua Wu Lihua Feng Huang Wu Lihong Wang Hengyi Xu Fen Fu |
| author_facet | Hua Wu Lihua Feng Huang Wu Lihong Wang Hengyi Xu Fen Fu |
| author_sort | Hua Wu |
| collection | DOAJ |
| description | Nanoplastics (NPs) are an emerging class of pollutants. They can act as a“Trojan horse” to change the bioavailability and toxicity of heavy metals in the environment. However, research on the combined toxicity of heavy metals and NPs is scarce, especially during the critical developmental period of adolescence. In this study, polystyrene nanoplastics (PS-NPs) and/or cadmium (Cd) were exposed to 4-week-old female rats for 28 days, with the aim of exploring the potential effects of combined exposure to PS-NPs and Cd on the ovaries of adolescence rats. Results showed that co-exposure to PS-NPs and Cd exacerbated ovarian toxicity in rats, primarily through increased atretic follicle numbers and endocrine disruption. Further studies revealed that PS-NPs and Cd synergistically repressed the SIRT3-SOD2/Gpx4 pathway, inducing mitochondrial oxidative stress and ferroptosis, resulting in damage to ovarian structure and function. However, the addition of the mitochondrion-targeted antioxidant SS-31 and the ferroptosis inhibitor Fer-1 reversed the harm to the ovaries from co-exposure to PS-NPs and Cd, the aberrant expression of genes related to the SIRT3-SOD2/Gpx4 pathway was also improved. Our results suggested that co-exposure to PS-NPs and Cd may trigger ferroptosis by inhibiting the SIRT3-SOD2/Gpx4 pathway, leading to mitochondrial redox imbalance, which provided novel insights into reproductive toxicity due to the interaction of PS-NPs and Cd during adolescence. |
| format | Article |
| id | doaj-art-931cb43f3f82455193f099a031b9593f |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-931cb43f3f82455193f099a031b9593f2025-02-12T05:30:01ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117622Synergistic effects of PS-NPs and Cd on ovarian toxicity in adolescent rats: Ferroptosis by induction of mitochondrial redox imbalance via the SIRT3-SOD2/Gpx4 pathwayHua Wu0Lihua Feng1Huang Wu2Lihong Wang3Hengyi Xu4Fen Fu5The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China; State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaThe Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China; State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaThe Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, ChinaThe Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China; Correspondence to: State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China; Correspondence to: The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang 330000, China.Nanoplastics (NPs) are an emerging class of pollutants. They can act as a“Trojan horse” to change the bioavailability and toxicity of heavy metals in the environment. However, research on the combined toxicity of heavy metals and NPs is scarce, especially during the critical developmental period of adolescence. In this study, polystyrene nanoplastics (PS-NPs) and/or cadmium (Cd) were exposed to 4-week-old female rats for 28 days, with the aim of exploring the potential effects of combined exposure to PS-NPs and Cd on the ovaries of adolescence rats. Results showed that co-exposure to PS-NPs and Cd exacerbated ovarian toxicity in rats, primarily through increased atretic follicle numbers and endocrine disruption. Further studies revealed that PS-NPs and Cd synergistically repressed the SIRT3-SOD2/Gpx4 pathway, inducing mitochondrial oxidative stress and ferroptosis, resulting in damage to ovarian structure and function. However, the addition of the mitochondrion-targeted antioxidant SS-31 and the ferroptosis inhibitor Fer-1 reversed the harm to the ovaries from co-exposure to PS-NPs and Cd, the aberrant expression of genes related to the SIRT3-SOD2/Gpx4 pathway was also improved. Our results suggested that co-exposure to PS-NPs and Cd may trigger ferroptosis by inhibiting the SIRT3-SOD2/Gpx4 pathway, leading to mitochondrial redox imbalance, which provided novel insights into reproductive toxicity due to the interaction of PS-NPs and Cd during adolescence.http://www.sciencedirect.com/science/article/pii/S0147651324016981PS-NPsCdAdolescent ovarian developmentFerroptosisSIRT3-SOD2/Gpx4 pathway |
| spellingShingle | Hua Wu Lihua Feng Huang Wu Lihong Wang Hengyi Xu Fen Fu Synergistic effects of PS-NPs and Cd on ovarian toxicity in adolescent rats: Ferroptosis by induction of mitochondrial redox imbalance via the SIRT3-SOD2/Gpx4 pathway Ecotoxicology and Environmental Safety PS-NPs Cd Adolescent ovarian development Ferroptosis SIRT3-SOD2/Gpx4 pathway |
| title | Synergistic effects of PS-NPs and Cd on ovarian toxicity in adolescent rats: Ferroptosis by induction of mitochondrial redox imbalance via the SIRT3-SOD2/Gpx4 pathway |
| title_full | Synergistic effects of PS-NPs and Cd on ovarian toxicity in adolescent rats: Ferroptosis by induction of mitochondrial redox imbalance via the SIRT3-SOD2/Gpx4 pathway |
| title_fullStr | Synergistic effects of PS-NPs and Cd on ovarian toxicity in adolescent rats: Ferroptosis by induction of mitochondrial redox imbalance via the SIRT3-SOD2/Gpx4 pathway |
| title_full_unstemmed | Synergistic effects of PS-NPs and Cd on ovarian toxicity in adolescent rats: Ferroptosis by induction of mitochondrial redox imbalance via the SIRT3-SOD2/Gpx4 pathway |
| title_short | Synergistic effects of PS-NPs and Cd on ovarian toxicity in adolescent rats: Ferroptosis by induction of mitochondrial redox imbalance via the SIRT3-SOD2/Gpx4 pathway |
| title_sort | synergistic effects of ps nps and cd on ovarian toxicity in adolescent rats ferroptosis by induction of mitochondrial redox imbalance via the sirt3 sod2 gpx4 pathway |
| topic | PS-NPs Cd Adolescent ovarian development Ferroptosis SIRT3-SOD2/Gpx4 pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324016981 |
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