5-Azacytidine induces early stage apoptosis and promotes in vitro maturation by changing chromosomal construction in murine oocytes
► 5-AzaC inhibits the condensation of chromosomes and induces chromosome instability. ► 5-AzaC induces early apoptosis and IVM in mouse oocytes. ► 5-AzaC increases the mRNA levels of caspase-3, caspase-8, caspase-9, gdf-9 and bmp-15. As an anticancer drug, 5-azacytidine (5-AzaC) has been widely used...
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| Veröffentlicht in: | Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2013-06, Vol.37, p.56-61 |
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| container_title | Reproductive toxicology (Elmsford, N.Y.) |
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| creator | Zhao, F.Y. Shao, C.P. Li, Y. Ma, W.Y. Tian, N. Zheng, J.H. |
| description | ► 5-AzaC inhibits the condensation of chromosomes and induces chromosome instability. ► 5-AzaC induces early apoptosis and IVM in mouse oocytes. ► 5-AzaC increases the mRNA levels of caspase-3, caspase-8, caspase-9, gdf-9 and bmp-15.
As an anticancer drug, 5-azacytidine (5-AzaC) has been widely used to treat various cancers. To investigate the effect of 5-AzaC on mouse oocytes cultured in vitro, we have performed morphological and molecular biology studies to examine the behavior of chromosomes and oocyte development. In 5-AzaC-treated oocytes, chromosomes were decondensed and unstable. The mRNA levels of Caspase3, Caspase8, and Caspase9 increased with the occurrence of early stage apoptosis in oocytes following 5-AzaC treatment. Furthermore, the mRNA levels of Gdf9 and Bmp15 also increased with the corresponding morphological changes in 5-AzaC-treated oocytes. In conclusion, 5-AzaC not only induced early apoptosis through both extrinsic and intrinsic pathways, but also had a positive effect on the developmental competence of mouse oocytes during in vitro maturation. These effects may be due to changes in chromosomal construction induced by DNA hypomethylation. |
| doi_str_mv | 10.1016/j.reprotox.2013.01.007 |
| format | Article |
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As an anticancer drug, 5-azacytidine (5-AzaC) has been widely used to treat various cancers. To investigate the effect of 5-AzaC on mouse oocytes cultured in vitro, we have performed morphological and molecular biology studies to examine the behavior of chromosomes and oocyte development. In 5-AzaC-treated oocytes, chromosomes were decondensed and unstable. The mRNA levels of Caspase3, Caspase8, and Caspase9 increased with the occurrence of early stage apoptosis in oocytes following 5-AzaC treatment. Furthermore, the mRNA levels of Gdf9 and Bmp15 also increased with the corresponding morphological changes in 5-AzaC-treated oocytes. In conclusion, 5-AzaC not only induced early apoptosis through both extrinsic and intrinsic pathways, but also had a positive effect on the developmental competence of mouse oocytes during in vitro maturation. These effects may be due to changes in chromosomal construction induced by DNA hypomethylation.</description><identifier>ISSN: 0890-6238</identifier><identifier>EISSN: 1873-1708</identifier><identifier>DOI: 10.1016/j.reprotox.2013.01.007</identifier><identifier>PMID: 23395740</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>5-Azacytidine ; Animals ; Antimetabolites, Antineoplastic - toxicity ; Apoptosis - drug effects ; Azacitidine - toxicity ; Caspases - genetics ; Cell Growth Processes - drug effects ; Cells, Cultured ; Chromosomes - metabolism ; Decondensation ; Early apoptosis ; Female ; Hypomethylation ; In vitro ; Maturation ; Mice ; Mouse ; Oocytes ; Oocytes - drug effects ; Oocytes - physiology ; RNA, Messenger - metabolism</subject><ispartof>Reproductive toxicology (Elmsford, N.Y.), 2013-06, Vol.37, p.56-61</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-25d55acf33143da5d5a43e601518edd449bdb324cb26d52156dee543d4d986b43</citedby><cites>FETCH-LOGICAL-c368t-25d55acf33143da5d5a43e601518edd449bdb324cb26d52156dee543d4d986b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.reprotox.2013.01.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23395740$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, F.Y.</creatorcontrib><creatorcontrib>Shao, C.P.</creatorcontrib><creatorcontrib>Li, Y.</creatorcontrib><creatorcontrib>Ma, W.Y.</creatorcontrib><creatorcontrib>Tian, N.</creatorcontrib><creatorcontrib>Zheng, J.H.</creatorcontrib><title>5-Azacytidine induces early stage apoptosis and promotes in vitro maturation by changing chromosomal construction in murine oocytes</title><title>Reproductive toxicology (Elmsford, N.Y.)</title><addtitle>Reprod Toxicol</addtitle><description>► 5-AzaC inhibits the condensation of chromosomes and induces chromosome instability. ► 5-AzaC induces early apoptosis and IVM in mouse oocytes. ► 5-AzaC increases the mRNA levels of caspase-3, caspase-8, caspase-9, gdf-9 and bmp-15.
As an anticancer drug, 5-azacytidine (5-AzaC) has been widely used to treat various cancers. To investigate the effect of 5-AzaC on mouse oocytes cultured in vitro, we have performed morphological and molecular biology studies to examine the behavior of chromosomes and oocyte development. In 5-AzaC-treated oocytes, chromosomes were decondensed and unstable. The mRNA levels of Caspase3, Caspase8, and Caspase9 increased with the occurrence of early stage apoptosis in oocytes following 5-AzaC treatment. Furthermore, the mRNA levels of Gdf9 and Bmp15 also increased with the corresponding morphological changes in 5-AzaC-treated oocytes. In conclusion, 5-AzaC not only induced early apoptosis through both extrinsic and intrinsic pathways, but also had a positive effect on the developmental competence of mouse oocytes during in vitro maturation. These effects may be due to changes in chromosomal construction induced by DNA hypomethylation.</description><subject>5-Azacytidine</subject><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - toxicity</subject><subject>Apoptosis - drug effects</subject><subject>Azacitidine - toxicity</subject><subject>Caspases - genetics</subject><subject>Cell Growth Processes - drug effects</subject><subject>Cells, Cultured</subject><subject>Chromosomes - metabolism</subject><subject>Decondensation</subject><subject>Early apoptosis</subject><subject>Female</subject><subject>Hypomethylation</subject><subject>In vitro</subject><subject>Maturation</subject><subject>Mice</subject><subject>Mouse</subject><subject>Oocytes</subject><subject>Oocytes - drug effects</subject><subject>Oocytes - physiology</subject><subject>RNA, Messenger - metabolism</subject><issn>0890-6238</issn><issn>1873-1708</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1uGyEURlHVqHaTvoLFspuZwPAzM7tGUdNEstRNs0YMXLtYM-ACY9XZ9sWL4yTbrADpfBzd-yG0oqSmhMrrXR1hH0MOf-uGUFYTWhPSfkBL2rWsoi3pPqIl6XpSyYZ1C_Q5pR0hhLd9-wktGsZ60XKyRP9EdfOkzTE76zxg5-1sIGHQcTzilPUWsN6HfQ7JJay9xUU6hVwQ5_HB5RjwpPMcdXbB4-GIzW_tt85vy-VEpjDpEZvgU46zeYZKcJrjyRZCEUO6QhcbPSb48nJeose7779u76v1zx8PtzfryjDZ5aoRVghtNoxRzqwuL80ZSEIF7cBazvvBDqzhZmikFQ0V0gKIgnLbd3Lg7BJ9Pf9bZvgzQ8pqcsnAOGoPYU6KMtpLykXbFlSeURNDShE2ah_dpONRUaJOBaidei1AnQpQhKpSQAmuXhzzMIF9i71uvADfzgCUSQ8OokrGgTdgXQSTlQ3uPcd_DUOemw</recordid><startdate>201306</startdate><enddate>201306</enddate><creator>Zhao, F.Y.</creator><creator>Shao, C.P.</creator><creator>Li, Y.</creator><creator>Ma, W.Y.</creator><creator>Tian, N.</creator><creator>Zheng, J.H.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201306</creationdate><title>5-Azacytidine induces early stage apoptosis and promotes in vitro maturation by changing chromosomal construction in murine oocytes</title><author>Zhao, F.Y. ; Shao, C.P. ; Li, Y. ; Ma, W.Y. ; Tian, N. ; Zheng, J.H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-25d55acf33143da5d5a43e601518edd449bdb324cb26d52156dee543d4d986b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>5-Azacytidine</topic><topic>Animals</topic><topic>Antimetabolites, Antineoplastic - toxicity</topic><topic>Apoptosis - drug effects</topic><topic>Azacitidine - toxicity</topic><topic>Caspases - genetics</topic><topic>Cell Growth Processes - drug effects</topic><topic>Cells, Cultured</topic><topic>Chromosomes - metabolism</topic><topic>Decondensation</topic><topic>Early apoptosis</topic><topic>Female</topic><topic>Hypomethylation</topic><topic>In vitro</topic><topic>Maturation</topic><topic>Mice</topic><topic>Mouse</topic><topic>Oocytes</topic><topic>Oocytes - drug effects</topic><topic>Oocytes - physiology</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, F.Y.</creatorcontrib><creatorcontrib>Shao, C.P.</creatorcontrib><creatorcontrib>Li, Y.</creatorcontrib><creatorcontrib>Ma, W.Y.</creatorcontrib><creatorcontrib>Tian, N.</creatorcontrib><creatorcontrib>Zheng, J.H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Reproductive toxicology (Elmsford, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, F.Y.</au><au>Shao, C.P.</au><au>Li, Y.</au><au>Ma, W.Y.</au><au>Tian, N.</au><au>Zheng, J.H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5-Azacytidine induces early stage apoptosis and promotes in vitro maturation by changing chromosomal construction in murine oocytes</atitle><jtitle>Reproductive toxicology (Elmsford, N.Y.)</jtitle><addtitle>Reprod Toxicol</addtitle><date>2013-06</date><risdate>2013</risdate><volume>37</volume><spage>56</spage><epage>61</epage><pages>56-61</pages><issn>0890-6238</issn><eissn>1873-1708</eissn><abstract>► 5-AzaC inhibits the condensation of chromosomes and induces chromosome instability. ► 5-AzaC induces early apoptosis and IVM in mouse oocytes. ► 5-AzaC increases the mRNA levels of caspase-3, caspase-8, caspase-9, gdf-9 and bmp-15.
As an anticancer drug, 5-azacytidine (5-AzaC) has been widely used to treat various cancers. To investigate the effect of 5-AzaC on mouse oocytes cultured in vitro, we have performed morphological and molecular biology studies to examine the behavior of chromosomes and oocyte development. In 5-AzaC-treated oocytes, chromosomes were decondensed and unstable. The mRNA levels of Caspase3, Caspase8, and Caspase9 increased with the occurrence of early stage apoptosis in oocytes following 5-AzaC treatment. Furthermore, the mRNA levels of Gdf9 and Bmp15 also increased with the corresponding morphological changes in 5-AzaC-treated oocytes. In conclusion, 5-AzaC not only induced early apoptosis through both extrinsic and intrinsic pathways, but also had a positive effect on the developmental competence of mouse oocytes during in vitro maturation. These effects may be due to changes in chromosomal construction induced by DNA hypomethylation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23395740</pmid><doi>10.1016/j.reprotox.2013.01.007</doi><tpages>6</tpages></addata></record> |
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| subjects | 5-Azacytidine Animals Antimetabolites, Antineoplastic - toxicity Apoptosis - drug effects Azacitidine - toxicity Caspases - genetics Cell Growth Processes - drug effects Cells, Cultured Chromosomes - metabolism Decondensation Early apoptosis Female Hypomethylation In vitro Maturation Mice Mouse Oocytes Oocytes - drug effects Oocytes - physiology RNA, Messenger - metabolism |
| title | 5-Azacytidine induces early stage apoptosis and promotes in vitro maturation by changing chromosomal construction in murine oocytes |
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