Revealing the core suppression effects of various Di (2-ethylhexyl) phthalate exposure on early meiosis progression in postnatal male mice via single-cell RNA sequencing
The male reproductive system has been the subject of considerable attention in recent years due to the adverse effects of Di (2-ethylhexyl) phthalate (DEHP). Although previous research has suggested that DEHP exposure hinders the early meiotic progression of male germ cells, the underlying mechanism...
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Elsevier
2025-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325002027 |
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| author | Baoquan Han Lei Hua Shuai Yu Wei Ge Cong Huang Yu Tian Chunxiao Li Jiamao Yan Tian Qiao Jiachen Guo Dongliang Lu Bin Wang Diya Cai Yunqi Zhang Shaolin Liang Jianjuan Zhao Qi Hou Wei Shen Zhongyi Sun |
| author_facet | Baoquan Han Lei Hua Shuai Yu Wei Ge Cong Huang Yu Tian Chunxiao Li Jiamao Yan Tian Qiao Jiachen Guo Dongliang Lu Bin Wang Diya Cai Yunqi Zhang Shaolin Liang Jianjuan Zhao Qi Hou Wei Shen Zhongyi Sun |
| author_sort | Baoquan Han |
| collection | DOAJ |
| description | The male reproductive system has been the subject of considerable attention in recent years due to the adverse effects of Di (2-ethylhexyl) phthalate (DEHP). Although previous research has suggested that DEHP exposure hinders the early meiotic progression of male germ cells, the underlying mechanisms are still not well understood. The transcriptomic changes in testicular cells of postnatal male rodents following DEHP exposure were meticulously analyzed using 10X Genomics single-cell RNA sequencing in this study. For downstream analysis, we acquired 42,000 cells and generated 3172,754,990 reads. DEHP exposure at concentrations of 40 μg/kg/day (DEHP40) and 80 μg/kg/day (DEHP80) substantially decreased the proportion of pachytene and diplotene spermatocytes, indicating a shared inhibitory effect on early meiosis, as demonstrated by our findings. In addition, DEHP exposure disrupted the cellular communication between Sertoli cells and germ cells, which had a significant impact on the p38-MAPK signaling pathway. The expression of key ligand genes Tgfb1 and Tgfb3 in Sertoli cells was significantly reduced. DEHP exposure resulted in a substantial decrease in the expression of the Trp53 gene, which in turn down-regulated three critical downstream genes (Stmn1, Tubb5, and Ccnb1) that are implicated in spindle organization from a mechanistic perspective. This study offers the first comprehensive evidence that DEHP inhibits early meiotic progression in male germ cells through the Trp53-mediated p38-MAPK pathway, providing crucial insights into the molecular mechanisms underlying DEHP-induced male reproductive toxicity. Our results emphasize the enduring negative effects of DEHP exposure on male fertility, which have substantial ramifications for the comprehension and mitigation of the influence of environmental estrogens on reproductive health. |
| format | Article |
| id | doaj-art-39920737447d4ec0a3a777294e381df7 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-39920737447d4ec0a3a777294e381df72025-02-10T04:33:29ZengElsevierEcotoxicology and Environmental Safety0147-65132025-02-01291117866Revealing the core suppression effects of various Di (2-ethylhexyl) phthalate exposure on early meiosis progression in postnatal male mice via single-cell RNA sequencingBaoquan Han0Lei Hua1Shuai Yu2Wei Ge3Cong Huang4Yu Tian5Chunxiao Li6Jiamao Yan7Tian Qiao8Jiachen Guo9Dongliang Lu10Bin Wang11Diya Cai12Yunqi Zhang13Shaolin Liang14Jianjuan Zhao15Qi Hou16Wei Shen17Zhongyi Sun18Department of Urology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China; College of Life Sciences, Qingdao Agricultural University, Qingdao, ChinaSchool of Clinical Medicine, Henan University, Kaifeng, ChinaQingdao Fengxi Pharmaceuticals Co., Ltd., Qingdao, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao, ChinaDepartment of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao, ChinaCollege of Life Sciences, Qingdao Agricultural University, Qingdao, ChinaDepartment of Urology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, ChinaDepartment of Urology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, ChinaDepartment of Urology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, ChinaSTI-Zhilian Research Institute for Innovation and Digital Health, Beijing, ChinaSTI-Zhilian Research Institute for Innovation and Digital Health, Beijing, China; Institute for Six-sector Economy, Fudan University, Shanghai, ChinaSTI-Zhilian Research Institute for Innovation and Digital Health, Beijing, ChinaDepartment of Urology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China; Corresponding authors.College of Life Sciences, Qingdao Agricultural University, Qingdao, China; Corresponding authors.Department of Urology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China; Corresponding authors.The male reproductive system has been the subject of considerable attention in recent years due to the adverse effects of Di (2-ethylhexyl) phthalate (DEHP). Although previous research has suggested that DEHP exposure hinders the early meiotic progression of male germ cells, the underlying mechanisms are still not well understood. The transcriptomic changes in testicular cells of postnatal male rodents following DEHP exposure were meticulously analyzed using 10X Genomics single-cell RNA sequencing in this study. For downstream analysis, we acquired 42,000 cells and generated 3172,754,990 reads. DEHP exposure at concentrations of 40 μg/kg/day (DEHP40) and 80 μg/kg/day (DEHP80) substantially decreased the proportion of pachytene and diplotene spermatocytes, indicating a shared inhibitory effect on early meiosis, as demonstrated by our findings. In addition, DEHP exposure disrupted the cellular communication between Sertoli cells and germ cells, which had a significant impact on the p38-MAPK signaling pathway. The expression of key ligand genes Tgfb1 and Tgfb3 in Sertoli cells was significantly reduced. DEHP exposure resulted in a substantial decrease in the expression of the Trp53 gene, which in turn down-regulated three critical downstream genes (Stmn1, Tubb5, and Ccnb1) that are implicated in spindle organization from a mechanistic perspective. This study offers the first comprehensive evidence that DEHP inhibits early meiotic progression in male germ cells through the Trp53-mediated p38-MAPK pathway, providing crucial insights into the molecular mechanisms underlying DEHP-induced male reproductive toxicity. Our results emphasize the enduring negative effects of DEHP exposure on male fertility, which have substantial ramifications for the comprehension and mitigation of the influence of environmental estrogens on reproductive health.http://www.sciencedirect.com/science/article/pii/S0147651325002027Di (2-ethylhexyl) phthalateEarly meiosisSingle-cell RNA sequencingP38 mitogen-activated protein kinase pathwayTrp53Reproductive toxicity |
| spellingShingle | Baoquan Han Lei Hua Shuai Yu Wei Ge Cong Huang Yu Tian Chunxiao Li Jiamao Yan Tian Qiao Jiachen Guo Dongliang Lu Bin Wang Diya Cai Yunqi Zhang Shaolin Liang Jianjuan Zhao Qi Hou Wei Shen Zhongyi Sun Revealing the core suppression effects of various Di (2-ethylhexyl) phthalate exposure on early meiosis progression in postnatal male mice via single-cell RNA sequencing Ecotoxicology and Environmental Safety Di (2-ethylhexyl) phthalate Early meiosis Single-cell RNA sequencing P38 mitogen-activated protein kinase pathway Trp53 Reproductive toxicity |
| title | Revealing the core suppression effects of various Di (2-ethylhexyl) phthalate exposure on early meiosis progression in postnatal male mice via single-cell RNA sequencing |
| title_full | Revealing the core suppression effects of various Di (2-ethylhexyl) phthalate exposure on early meiosis progression in postnatal male mice via single-cell RNA sequencing |
| title_fullStr | Revealing the core suppression effects of various Di (2-ethylhexyl) phthalate exposure on early meiosis progression in postnatal male mice via single-cell RNA sequencing |
| title_full_unstemmed | Revealing the core suppression effects of various Di (2-ethylhexyl) phthalate exposure on early meiosis progression in postnatal male mice via single-cell RNA sequencing |
| title_short | Revealing the core suppression effects of various Di (2-ethylhexyl) phthalate exposure on early meiosis progression in postnatal male mice via single-cell RNA sequencing |
| title_sort | revealing the core suppression effects of various di 2 ethylhexyl phthalate exposure on early meiosis progression in postnatal male mice via single cell rna sequencing |
| topic | Di (2-ethylhexyl) phthalate Early meiosis Single-cell RNA sequencing P38 mitogen-activated protein kinase pathway Trp53 Reproductive toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325002027 |
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