Microcystin-LR accelerates follicular atresia in mice via JNK-mediated adherent junction damage of ovarian granulosa cells
Microcystin-LR (MC-LR), one of aquatic environmental contaminants with reproductive toxicity produced by cyanobacterial blooms, but its toxic effects and mechanisms on the ovary are not fully understood. Here, proteomic techniques and molecular biology experiments were performed to study the potenti...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323000969 |
| _version_ | 1828012100839014400 |
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| author | Xingde Du Yu Fu Zhihui Tian Haohao Liu Hongxia Xin Xiaoli Fu Fufang Wang Huizhen Zhang Xin Zeng |
| author_facet | Xingde Du Yu Fu Zhihui Tian Haohao Liu Hongxia Xin Xiaoli Fu Fufang Wang Huizhen Zhang Xin Zeng |
| author_sort | Xingde Du |
| collection | DOAJ |
| description | Microcystin-LR (MC-LR), one of aquatic environmental contaminants with reproductive toxicity produced by cyanobacterial blooms, but its toxic effects and mechanisms on the ovary are not fully understood. Here, proteomic techniques and molecular biology experiments were performed to study the potential mechanism of MC-LR-caused ovarian toxicity. Results showed that protein expression profile of ovarian granulosa cells (KK-1) was changed by 17 μg/mL MC-LR exposure. Comparing with the control group, 118 upregulated proteins as well as 97 downregulated proteins were identified in MC-LR group. Function of differentially expressed proteins was found to be enriched in pathways related to adherent junction, such as cadherin binding, cell-cell junction, cell adhesion and focal adherens. Furthermore, in vitro experiments, MC-LR significantly downregulated the expression levels of proteins associated with adherent junction (β-catenin, N-cadherin, and α-catenin) as well as caused cytoskeletal disruption in KK-1 cells (P < 0.05), indicating that the adherent junction was damaged. Results of in vivo experiments have shown that after 14 days of acute MC-LR exposure (40 μg/kg), damaged adherent junction and an increased number of atretic follicles were observed in mouse ovaries. Moreover, MC-LR activated JNK, an upstream regulator of adherent junction proteins, in KK-1 cells and mouse ovarian tissues. In contrast, JNK inhibition alleviated MC-LR-induced adherent junction damage in vivo and in vitro, as well as the number of atretic follicles. Taken together, findings from the present study indicated that JNK is involved in MC-LR-induced granulosa cell adherent junction damage, which accelerated follicular atresia. Our study clarified a novel mechanism of MC-LR-caused ovarian toxicity, providing a theoretical foundation for protecting female reproductive health from environmental pollutants. |
| first_indexed | 2024-04-10T09:26:26Z |
| format | Article |
| id | doaj.art-56a9dc503f92467280cc202c69f16834 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-10T09:26:26Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-56a9dc503f92467280cc202c69f168342023-02-20T04:08:36ZengElsevierEcotoxicology and Environmental Safety0147-65132023-03-01252114592Microcystin-LR accelerates follicular atresia in mice via JNK-mediated adherent junction damage of ovarian granulosa cellsXingde Du0Yu Fu1Zhihui Tian2Haohao Liu3Hongxia Xin4Xiaoli Fu5Fufang Wang6Huizhen Zhang7Xin Zeng8College of Public Health, Zhengzhou University, Zhengzhou 450001, ChinaCollege of Public Health, Zhengzhou University, Zhengzhou 450001, ChinaCollege of Public Health, Zhengzhou University, Zhengzhou 450001, ChinaCollege of Public Health, Zhengzhou University, Zhengzhou 450001, ChinaHenan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, ChinaCollege of Public Health, Zhengzhou University, Zhengzhou 450001, ChinaCollege of Public Health, Zhengzhou University, Zhengzhou 450001, ChinaCollege of Public Health, Zhengzhou University, Zhengzhou 450001, China; Corresponding authors.College of Public Health, Zhengzhou University, Zhengzhou 450001, China; Corresponding authors.Microcystin-LR (MC-LR), one of aquatic environmental contaminants with reproductive toxicity produced by cyanobacterial blooms, but its toxic effects and mechanisms on the ovary are not fully understood. Here, proteomic techniques and molecular biology experiments were performed to study the potential mechanism of MC-LR-caused ovarian toxicity. Results showed that protein expression profile of ovarian granulosa cells (KK-1) was changed by 17 μg/mL MC-LR exposure. Comparing with the control group, 118 upregulated proteins as well as 97 downregulated proteins were identified in MC-LR group. Function of differentially expressed proteins was found to be enriched in pathways related to adherent junction, such as cadherin binding, cell-cell junction, cell adhesion and focal adherens. Furthermore, in vitro experiments, MC-LR significantly downregulated the expression levels of proteins associated with adherent junction (β-catenin, N-cadherin, and α-catenin) as well as caused cytoskeletal disruption in KK-1 cells (P < 0.05), indicating that the adherent junction was damaged. Results of in vivo experiments have shown that after 14 days of acute MC-LR exposure (40 μg/kg), damaged adherent junction and an increased number of atretic follicles were observed in mouse ovaries. Moreover, MC-LR activated JNK, an upstream regulator of adherent junction proteins, in KK-1 cells and mouse ovarian tissues. In contrast, JNK inhibition alleviated MC-LR-induced adherent junction damage in vivo and in vitro, as well as the number of atretic follicles. Taken together, findings from the present study indicated that JNK is involved in MC-LR-induced granulosa cell adherent junction damage, which accelerated follicular atresia. Our study clarified a novel mechanism of MC-LR-caused ovarian toxicity, providing a theoretical foundation for protecting female reproductive health from environmental pollutants.http://www.sciencedirect.com/science/article/pii/S0147651323000969Microcystin-leucine arginineProteomicsAdherent junctionC-Jun N-terminal kinaseFollicular atresia |
| spellingShingle | Xingde Du Yu Fu Zhihui Tian Haohao Liu Hongxia Xin Xiaoli Fu Fufang Wang Huizhen Zhang Xin Zeng Microcystin-LR accelerates follicular atresia in mice via JNK-mediated adherent junction damage of ovarian granulosa cells Ecotoxicology and Environmental Safety Microcystin-leucine arginine Proteomics Adherent junction C-Jun N-terminal kinase Follicular atresia |
| title | Microcystin-LR accelerates follicular atresia in mice via JNK-mediated adherent junction damage of ovarian granulosa cells |
| title_full | Microcystin-LR accelerates follicular atresia in mice via JNK-mediated adherent junction damage of ovarian granulosa cells |
| title_fullStr | Microcystin-LR accelerates follicular atresia in mice via JNK-mediated adherent junction damage of ovarian granulosa cells |
| title_full_unstemmed | Microcystin-LR accelerates follicular atresia in mice via JNK-mediated adherent junction damage of ovarian granulosa cells |
| title_short | Microcystin-LR accelerates follicular atresia in mice via JNK-mediated adherent junction damage of ovarian granulosa cells |
| title_sort | microcystin lr accelerates follicular atresia in mice via jnk mediated adherent junction damage of ovarian granulosa cells |
| topic | Microcystin-leucine arginine Proteomics Adherent junction C-Jun N-terminal kinase Follicular atresia |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323000969 |
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