Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT Pathway
The effects of zearalenone (ZEA), a fungal toxin in food and feed, remain unclear on the mammary gland and lactation. This study examines ZEA-induced damage in lactating mice and bovine mammary epithelial cells (MAC-T), focusing on the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K...
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MDPI AG
2025-04-01
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| author | Hong Chen Di Qiu Xue Miao Wenyue Yang Qi He Hao Ren Luyao Zhang Hongri Ruan Jiantao Zhang Na Zhang |
| author_facet | Hong Chen Di Qiu Xue Miao Wenyue Yang Qi He Hao Ren Luyao Zhang Hongri Ruan Jiantao Zhang Na Zhang |
| author_sort | Hong Chen |
| collection | DOAJ |
| description | The effects of zearalenone (ZEA), a fungal toxin in food and feed, remain unclear on the mammary gland and lactation. This study examines ZEA-induced damage in lactating mice and bovine mammary epithelial cells (MAC-T), focusing on the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway in regulating cell proliferation and apoptosis. The results demonstrated that exposure to ZEA at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg) reduced lactation in female mice and slowed weight gain in their offspring. Hematoxylin and eosin (HE) staining and CSNK immunofluorescence staining of mammary tissue confirmed ZEA-induced mammary gland damage in vivo. Further analysis using PCNA immunohistochemistry and fluorescent TUNEL staining revealed that ZEA promoted apoptosis and decreased the proliferative capacity of mammary tissues. In vitro, 20 μM ZEA decreased MAC-T cell proliferation, increased apoptosis and oxidative stress, inhibited PI3K/AKT signaling, and decreased κ-casein (CSNK) expression. Pretreatment with a reactive oxygen species (ROS) scavenger (NAC) or PI3K/AKT activator (740-Y-P) reversed these effects, with NAC specifically restoring PI3K/AKT activity inhibited by ZEA. Overall, this study concludes that ZEA induces MAC-T cell apoptosis and disrupts proliferation via the ROS-mediated PI3K/AKT pathway, ultimately impairing lactation function. These findings highlight potential targets for managing ZEA contamination in food and its impact on lactation. |
| format | Article |
| id | doaj-art-64aab4830d2e442f959f62dc90c5f6de |
| institution | OA Journals |
| issn | 2076-2615 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Animals |
| spelling | doaj-art-64aab4830d2e442f959f62dc90c5f6de2025-08-20T02:09:18ZengMDPI AGAnimals2076-26152025-04-01157105010.3390/ani15071050Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT PathwayHong Chen0Di Qiu1Xue Miao2Wenyue Yang3Qi He4Hao Ren5Luyao Zhang6Hongri Ruan7Jiantao Zhang8Na Zhang9College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, ChinaKey Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, ChinaThe effects of zearalenone (ZEA), a fungal toxin in food and feed, remain unclear on the mammary gland and lactation. This study examines ZEA-induced damage in lactating mice and bovine mammary epithelial cells (MAC-T), focusing on the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway in regulating cell proliferation and apoptosis. The results demonstrated that exposure to ZEA at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg) reduced lactation in female mice and slowed weight gain in their offspring. Hematoxylin and eosin (HE) staining and CSNK immunofluorescence staining of mammary tissue confirmed ZEA-induced mammary gland damage in vivo. Further analysis using PCNA immunohistochemistry and fluorescent TUNEL staining revealed that ZEA promoted apoptosis and decreased the proliferative capacity of mammary tissues. In vitro, 20 μM ZEA decreased MAC-T cell proliferation, increased apoptosis and oxidative stress, inhibited PI3K/AKT signaling, and decreased κ-casein (CSNK) expression. Pretreatment with a reactive oxygen species (ROS) scavenger (NAC) or PI3K/AKT activator (740-Y-P) reversed these effects, with NAC specifically restoring PI3K/AKT activity inhibited by ZEA. Overall, this study concludes that ZEA induces MAC-T cell apoptosis and disrupts proliferation via the ROS-mediated PI3K/AKT pathway, ultimately impairing lactation function. These findings highlight potential targets for managing ZEA contamination in food and its impact on lactation.https://www.mdpi.com/2076-2615/15/7/1050mammary glandmilk productionoxidative stressproliferationzearalenone |
| spellingShingle | Hong Chen Di Qiu Xue Miao Wenyue Yang Qi He Hao Ren Luyao Zhang Hongri Ruan Jiantao Zhang Na Zhang Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT Pathway Animals mammary gland milk production oxidative stress proliferation zearalenone |
| title | Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT Pathway |
| title_full | Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT Pathway |
| title_fullStr | Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT Pathway |
| title_full_unstemmed | Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT Pathway |
| title_short | Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT Pathway |
| title_sort | zearalenone depresses lactation capacity through the ros mediated pi3k akt pathway |
| topic | mammary gland milk production oxidative stress proliferation zearalenone |
| url | https://www.mdpi.com/2076-2615/15/7/1050 |
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