Silica nanoparticles induce male reproductive toxicity via Crem hypermethylation mediated spermatocyte apoptosis and sperm flagella damage
Exposure to silica nanoparticles (SiNPs) could causally contribute to malfunctioning of the spermatogenesis, but the underlying mechanism is rarely known. This study was designed to explore the mechanism of Crem hypermethylation in SiNP-induced reproductive toxicity. The male mice were exposure to S...
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| description | Exposure to silica nanoparticles (SiNPs) could causally contribute to malfunctioning of the spermatogenesis, but the underlying mechanism is rarely known. This study was designed to explore the mechanism of
Crem
hypermethylation in SiNP-induced reproductive toxicity. The male mice were exposure to SiNPs (0 and 20 mg/kg·bw) once every 5 days via intratracheal instillation for 35 days. After exposure stopped, half of each group was killed, and the rest were sacrificed after another 15-day feeding. GC-2 cells were treated with 0 and 20 μg/mL SiNPs. The results showed that SiNPs led to structure damage of spermatocyte and sperm, caused spermatocyte apoptosis, and decreased sperm quantity and quality. After 15 days of the withdrawal, the testicular tissue damage gradually recovered. Mechanistic study showed that SiNPs induced hypermethylation of the gene of cAMP responsive element modulator (
Crem
) in the promoter region. Downregulation of Crem inhibited the expression of outer dense fiber 1 (Odf1), resulting in abnormal sperm flagella structure; at the same time, Crem inhibited the expression of Bcl-xl, causing upregulation of cytochrome-C, cleaved-caspase-9/caspase-9, cleaved-caspase-3/caspase-3, resulting in mitochondrial dependent apoptotic pathway. However, 5-aza, DNA methylation inhibitor, could reverse the SiNP-induced downregulation of Crem and reverse the Crem/Bcl-xl-mediated mitochondrial dependent apoptotic pathway. These results suggested SiNPs could disrupt spermatogenesis by causing Crem hypermethylation to regulate the Odf1 and Bcl-xl in spermatocytes resulting in the sperm flagella structure and spermatocyte apoptosis. Our study provided new insights into the male reproductive toxicity mechanism of SiNPs;
Crem
demethylation may be a potential way to prevent reproductive dysfunction from SiNP exposure. |
| doi_str_mv | 10.1007/s11356-024-32046-1 |
| format | Article |
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Crem
hypermethylation in SiNP-induced reproductive toxicity. The male mice were exposure to SiNPs (0 and 20 mg/kg·bw) once every 5 days via intratracheal instillation for 35 days. After exposure stopped, half of each group was killed, and the rest were sacrificed after another 15-day feeding. GC-2 cells were treated with 0 and 20 μg/mL SiNPs. The results showed that SiNPs led to structure damage of spermatocyte and sperm, caused spermatocyte apoptosis, and decreased sperm quantity and quality. After 15 days of the withdrawal, the testicular tissue damage gradually recovered. Mechanistic study showed that SiNPs induced hypermethylation of the gene of cAMP responsive element modulator (
Crem
) in the promoter region. Downregulation of Crem inhibited the expression of outer dense fiber 1 (Odf1), resulting in abnormal sperm flagella structure; at the same time, Crem inhibited the expression of Bcl-xl, causing upregulation of cytochrome-C, cleaved-caspase-9/caspase-9, cleaved-caspase-3/caspase-3, resulting in mitochondrial dependent apoptotic pathway. However, 5-aza, DNA methylation inhibitor, could reverse the SiNP-induced downregulation of Crem and reverse the Crem/Bcl-xl-mediated mitochondrial dependent apoptotic pathway. These results suggested SiNPs could disrupt spermatogenesis by causing Crem hypermethylation to regulate the Odf1 and Bcl-xl in spermatocytes resulting in the sperm flagella structure and spermatocyte apoptosis. Our study provided new insights into the male reproductive toxicity mechanism of SiNPs;
Crem
demethylation may be a potential way to prevent reproductive dysfunction from SiNP exposure.</description><identifier>ISSN: 1614-7499</identifier><identifier>ISSN: 0944-1344</identifier><identifier>EISSN: 1614-7499</identifier><identifier>DOI: 10.1007/s11356-024-32046-1</identifier><identifier>PMID: 38265582</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Apoptosis ; Aquatic Pollution ; Atmospheric Protection/Air Quality Control/Air Pollution ; Bcl-x protein ; Caspase-3 ; Caspase-9 ; Cyclic AMP response element modulator ; Cytochrome c ; Damage ; Demethylation ; DNA methylation ; Down-regulation ; Earth and Environmental Science ; Ecotoxicology ; Environment ; Environmental Chemistry ; Environmental Health ; Exposure ; Flagella ; flagellum ; Gametocytes ; genes ; Males ; mitochondria ; Nanoparticles ; promoter regions ; Regulatory sequences ; reproductive toxicology ; Research Article ; Silica ; Silicon dioxide ; Sperm ; Spermatocytes ; Spermatogenesis ; spermatozoa ; testes ; Toxicity ; Trachea ; Waste Water Technology ; Water Management ; Water Pollution Control</subject><ispartof>Environmental science and pollution research international, 2024-02, Vol.31 (9), p.13856-13866</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c359t-e6cba827cbaca1d0da1e2d82e7c7e642117156e6c4ae5b9faa7fcc62caa8f0703</cites><orcidid>0000-0002-6549-2400</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11356-024-32046-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11356-024-32046-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38265582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sang, Yujian</creatorcontrib><creatorcontrib>Liu, Jianhui</creatorcontrib><creatorcontrib>Dong, Xiaomin</creatorcontrib><creatorcontrib>Gao, Leqiang</creatorcontrib><creatorcontrib>Li, Xiangyang</creatorcontrib><creatorcontrib>Zhou, Guiqing</creatorcontrib><creatorcontrib>Zhang, Yue</creatorcontrib><creatorcontrib>Xue, Jinglong</creatorcontrib><creatorcontrib>Zhao, Moxuan</creatorcontrib><creatorcontrib>Zhou, Xianqing</creatorcontrib><title>Silica nanoparticles induce male reproductive toxicity via Crem hypermethylation mediated spermatocyte apoptosis and sperm flagella damage</title><title>Environmental science and pollution research international</title><addtitle>Environ Sci Pollut Res</addtitle><addtitle>Environ Sci Pollut Res Int</addtitle><description>Exposure to silica nanoparticles (SiNPs) could causally contribute to malfunctioning of the spermatogenesis, but the underlying mechanism is rarely known. This study was designed to explore the mechanism of
Crem
hypermethylation in SiNP-induced reproductive toxicity. The male mice were exposure to SiNPs (0 and 20 mg/kg·bw) once every 5 days via intratracheal instillation for 35 days. After exposure stopped, half of each group was killed, and the rest were sacrificed after another 15-day feeding. GC-2 cells were treated with 0 and 20 μg/mL SiNPs. The results showed that SiNPs led to structure damage of spermatocyte and sperm, caused spermatocyte apoptosis, and decreased sperm quantity and quality. After 15 days of the withdrawal, the testicular tissue damage gradually recovered. Mechanistic study showed that SiNPs induced hypermethylation of the gene of cAMP responsive element modulator (
Crem
) in the promoter region. Downregulation of Crem inhibited the expression of outer dense fiber 1 (Odf1), resulting in abnormal sperm flagella structure; at the same time, Crem inhibited the expression of Bcl-xl, causing upregulation of cytochrome-C, cleaved-caspase-9/caspase-9, cleaved-caspase-3/caspase-3, resulting in mitochondrial dependent apoptotic pathway. However, 5-aza, DNA methylation inhibitor, could reverse the SiNP-induced downregulation of Crem and reverse the Crem/Bcl-xl-mediated mitochondrial dependent apoptotic pathway. These results suggested SiNPs could disrupt spermatogenesis by causing Crem hypermethylation to regulate the Odf1 and Bcl-xl in spermatocytes resulting in the sperm flagella structure and spermatocyte apoptosis. Our study provided new insights into the male reproductive toxicity mechanism of SiNPs;
Crem
demethylation may be a potential way to prevent reproductive dysfunction from SiNP exposure.</description><subject>Apoptosis</subject><subject>Aquatic Pollution</subject><subject>Atmospheric Protection/Air Quality Control/Air Pollution</subject><subject>Bcl-x protein</subject><subject>Caspase-3</subject><subject>Caspase-9</subject><subject>Cyclic AMP response element modulator</subject><subject>Cytochrome c</subject><subject>Damage</subject><subject>Demethylation</subject><subject>DNA methylation</subject><subject>Down-regulation</subject><subject>Earth and Environmental Science</subject><subject>Ecotoxicology</subject><subject>Environment</subject><subject>Environmental Chemistry</subject><subject>Environmental Health</subject><subject>Exposure</subject><subject>Flagella</subject><subject>flagellum</subject><subject>Gametocytes</subject><subject>genes</subject><subject>Males</subject><subject>mitochondria</subject><subject>Nanoparticles</subject><subject>promoter regions</subject><subject>Regulatory sequences</subject><subject>reproductive toxicology</subject><subject>Research Article</subject><subject>Silica</subject><subject>Silicon dioxide</subject><subject>Sperm</subject><subject>Spermatocytes</subject><subject>Spermatogenesis</subject><subject>spermatozoa</subject><subject>testes</subject><subject>Toxicity</subject><subject>Trachea</subject><subject>Waste Water Technology</subject><subject>Water Management</subject><subject>Water Pollution 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nanoparticles induce male reproductive toxicity via Crem hypermethylation mediated spermatocyte apoptosis and sperm flagella damage</title><author>Sang, Yujian ; Liu, Jianhui ; Dong, Xiaomin ; Gao, Leqiang ; Li, Xiangyang ; Zhou, Guiqing ; Zhang, Yue ; Xue, Jinglong ; Zhao, Moxuan ; Zhou, Xianqing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-e6cba827cbaca1d0da1e2d82e7c7e642117156e6c4ae5b9faa7fcc62caa8f0703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Apoptosis</topic><topic>Aquatic Pollution</topic><topic>Atmospheric Protection/Air Quality Control/Air Pollution</topic><topic>Bcl-x protein</topic><topic>Caspase-3</topic><topic>Caspase-9</topic><topic>Cyclic AMP response element modulator</topic><topic>Cytochrome c</topic><topic>Damage</topic><topic>Demethylation</topic><topic>DNA methylation</topic><topic>Down-regulation</topic><topic>Earth and Environmental 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Jianhui</au><au>Dong, Xiaomin</au><au>Gao, Leqiang</au><au>Li, Xiangyang</au><au>Zhou, Guiqing</au><au>Zhang, Yue</au><au>Xue, Jinglong</au><au>Zhao, Moxuan</au><au>Zhou, Xianqing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Silica nanoparticles induce male reproductive toxicity via Crem hypermethylation mediated spermatocyte apoptosis and sperm flagella damage</atitle><jtitle>Environmental science and pollution research international</jtitle><stitle>Environ Sci Pollut Res</stitle><addtitle>Environ Sci Pollut Res Int</addtitle><date>2024-02-01</date><risdate>2024</risdate><volume>31</volume><issue>9</issue><spage>13856</spage><epage>13866</epage><pages>13856-13866</pages><issn>1614-7499</issn><issn>0944-1344</issn><eissn>1614-7499</eissn><abstract>Exposure to silica nanoparticles (SiNPs) could causally contribute to malfunctioning of the spermatogenesis, but the underlying mechanism is rarely known. This study was designed to explore the mechanism of
Crem
hypermethylation in SiNP-induced reproductive toxicity. The male mice were exposure to SiNPs (0 and 20 mg/kg·bw) once every 5 days via intratracheal instillation for 35 days. After exposure stopped, half of each group was killed, and the rest were sacrificed after another 15-day feeding. GC-2 cells were treated with 0 and 20 μg/mL SiNPs. The results showed that SiNPs led to structure damage of spermatocyte and sperm, caused spermatocyte apoptosis, and decreased sperm quantity and quality. After 15 days of the withdrawal, the testicular tissue damage gradually recovered. Mechanistic study showed that SiNPs induced hypermethylation of the gene of cAMP responsive element modulator (
Crem
) in the promoter region. Downregulation of Crem inhibited the expression of outer dense fiber 1 (Odf1), resulting in abnormal sperm flagella structure; at the same time, Crem inhibited the expression of Bcl-xl, causing upregulation of cytochrome-C, cleaved-caspase-9/caspase-9, cleaved-caspase-3/caspase-3, resulting in mitochondrial dependent apoptotic pathway. However, 5-aza, DNA methylation inhibitor, could reverse the SiNP-induced downregulation of Crem and reverse the Crem/Bcl-xl-mediated mitochondrial dependent apoptotic pathway. These results suggested SiNPs could disrupt spermatogenesis by causing Crem hypermethylation to regulate the Odf1 and Bcl-xl in spermatocytes resulting in the sperm flagella structure and spermatocyte apoptosis. Our study provided new insights into the male reproductive toxicity mechanism of SiNPs;
Crem
demethylation may be a potential way to prevent reproductive dysfunction from SiNP exposure.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38265582</pmid><doi>10.1007/s11356-024-32046-1</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6549-2400</orcidid></addata></record> |
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| subjects | Apoptosis Aquatic Pollution Atmospheric Protection/Air Quality Control/Air Pollution Bcl-x protein Caspase-3 Caspase-9 Cyclic AMP response element modulator Cytochrome c Damage Demethylation DNA methylation Down-regulation Earth and Environmental Science Ecotoxicology Environment Environmental Chemistry Environmental Health Exposure Flagella flagellum Gametocytes genes Males mitochondria Nanoparticles promoter regions Regulatory sequences reproductive toxicology Research Article Silica Silicon dioxide Sperm Spermatocytes Spermatogenesis spermatozoa testes Toxicity Trachea Waste Water Technology Water Management Water Pollution Control |
| title | Silica nanoparticles induce male reproductive toxicity via Crem hypermethylation mediated spermatocyte apoptosis and sperm flagella damage |
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