Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model
This study aimed to construct a working model for detecting the mitochondrial damage and expression of Mfn2. It furthermore explored the pathogenesis of premature ovarian failure (POF) induced by cisplatin. Forty young female mice were divided randomly into two groups. The first was the treatment gr...
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| description | This study aimed to construct a working model for detecting the mitochondrial damage and expression of Mfn2. It furthermore explored the pathogenesis of premature ovarian failure (POF) induced by cisplatin.
Forty young female mice were divided randomly into two groups. The first was the treatment group intraperitoneally administered cisplatin (1.5mg/kg). The untreated control group was likewise injected with physiological saline for 10 days. One month later, we observed the ovarian weight and morphological changes, particularly the development of follicles and concentration of sex hormones. Immunohistochemistry and western blotting were used to measure the two groups. We later evaluated ovarian cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels. We used transmission electron microscopy in order to observe the ultrastructure of ovarian cells. The phosphomolybdic acid colorimetric method was used to measure the ATP content in the ovarian tissue. Finally, the mitochondrial membrane potential of ovarian cells was detected with JC-1 dye.
The cisplatin resulted in a decline of body weight, reduced ovarian weight significantly, and resulted in disorders of the extrous cycle. The follicles' number decreased within the tissue's stromal hyperplasia. Moreover, E2 levels were reduced, and elevated gonadotropin levels were observed. However, Mfn2 was present in the cell's cytoplasm in both groups. Nevertheless, the Mfn2 levels and the expression of Bcl-2 were significantly decreased (p |
| doi_str_mv | 10.1371/journal.pone.0136421 |
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| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1708925437</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A427623100</galeid><doaj_id>oai_doaj_org_article_fc837364190f46d2b706bce0d6bdb8a1</doaj_id><sourcerecordid>A427623100</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-ddd635b5bae14d5de46de6aff1326dbb6458632db4e2ce37b92d7741f27181ba3</originalsourceid><addsrcrecordid>eNqNk99u0zAUxiMEYmPwBggsISG4aPG_OMkNUjU2qNSqCAa3lhOftK7SuNjONl6A58ZZs6pFu0C5cGz_vu_4HPskyUuCx4Rl5MPadq5VzXhrWxhjwgSn5FFySgpGR4Ji9vjg_yR55v0a45TlQjxNTqhgNOMsP03-zOwNurjdOvDe2BbZGs3rlqKpRxPvbWVUAI1uTFihuQm2WtlWO6Ma9Elt1BKQajWabO02WG98r15cq7jfoivjfQcemRaFFaCvDjYqdA72wKUyTT-fWw3N8-RJrRoPL4bxLPlxeXF1_mU0W3yenk9mo0oUNIy01oKlZVoqIFynGrjQIFRdE0aFLkvB0zympksOtAKWlQXVWcZJTTOSk1Kxs-T1znfbWC-HEnpJMpwXNOUsi8R0R2ir1nLrzEa539IqI-8WrFtK5YKpGpB1lUeB4KTAdTwILTMsygqwFqUuc0Wi18chWlduQFfQBqeaI9Pjndas5NJeS56mIiU8GrwbDJz9FasZ5Mb4CppGtWC7u3MXrEhx0cd68w_6cHYDtVQxAdPWNsatelM54TQTlBGMIzV-gIqfho2p4nurTVw_Erw_EkQmwG1Yqs57Of3-7f_Zxc9j9u0BuwLVhJW3TRfiU_XHIN-BlbPeO6j3RSZY9u1yXw3Zt4sc2iXKXh1e0F503x_sLz9rEJ4</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1708925437</pqid></control><display><type>article</type><title>Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Chen, Wenqi ; Xu, Xiaoyan ; Wang, Lingjuan ; Bai, Ge ; Xiang, Wenpei</creator><contributor>Zhang, Baohong</contributor><creatorcontrib>Chen, Wenqi ; Xu, Xiaoyan ; Wang, Lingjuan ; Bai, Ge ; Xiang, Wenpei ; Zhang, Baohong</creatorcontrib><description>This study aimed to construct a working model for detecting the mitochondrial damage and expression of Mfn2. It furthermore explored the pathogenesis of premature ovarian failure (POF) induced by cisplatin.
Forty young female mice were divided randomly into two groups. The first was the treatment group intraperitoneally administered cisplatin (1.5mg/kg). The untreated control group was likewise injected with physiological saline for 10 days. One month later, we observed the ovarian weight and morphological changes, particularly the development of follicles and concentration of sex hormones. Immunohistochemistry and western blotting were used to measure the two groups. We later evaluated ovarian cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels. We used transmission electron microscopy in order to observe the ultrastructure of ovarian cells. The phosphomolybdic acid colorimetric method was used to measure the ATP content in the ovarian tissue. Finally, the mitochondrial membrane potential of ovarian cells was detected with JC-1 dye.
The cisplatin resulted in a decline of body weight, reduced ovarian weight significantly, and resulted in disorders of the extrous cycle. The follicles' number decreased within the tissue's stromal hyperplasia. Moreover, E2 levels were reduced, and elevated gonadotropin levels were observed. However, Mfn2 was present in the cell's cytoplasm in both groups. Nevertheless, the Mfn2 levels and the expression of Bcl-2 were significantly decreased (p<0.05), but the expression of Bax and the apoptosis index (AI) was increased. In addition, the ATP levels (35.2 ± 5.7 μmol/g) of the control group were significantly higher (13.5 ± 3.8 μmol/g). Lastly, an obvious impairment of mitochondrial function and structure was observed.
The intreperitoneal injection of cisplatin, when administered for 10 days, establishes a POF model. Thus, the above results suggest that lower expression of Mfn2 may be involved in the mechanism of premature ovarian failure by affecting both the mitochondria's energy metabolism and its apoptosis. This decides the termination of the follicles' development.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0136421</identifier><identifier>PMID: 26327438</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal tissues ; Animals ; Apoptosis ; Apoptosis - physiology ; ATP ; Bax protein ; Bcl-2 protein ; Body weight ; Cell cycle ; Cisplatin ; Cisplatin - pharmacology ; Colorimetry ; Cytoplasm ; Damage detection ; Disease Models, Animal ; Electron microscopy ; Embryos ; Endoplasmic reticulum ; Energy metabolism ; Failure ; Family planning ; Female ; Follicles ; Gene expression ; Genetic aspects ; Gonadotropins ; GTP Phosphohydrolases - deficiency ; GTP Phosphohydrolases - physiology ; Health aspects ; Hormones ; Hyperplasia ; Immunohistochemistry ; In Situ Nick-End Labeling ; Membrane potential ; Membrane Potential, Mitochondrial - physiology ; Metabolism ; Mice ; Microscopy, Electron, Transmission ; Mitochondria ; Mitochondria - physiology ; Mitochondrial DNA ; Ovarian diseases ; Ovary - metabolism ; Ovary - physiopathology ; Ovary - ultrastructure ; Pathogenesis ; Phosphomolybdic acid ; Pituitary (anterior) ; Primary Ovarian Insufficiency - chemically induced ; Primary Ovarian Insufficiency - physiopathology ; Properties ; Real-Time Polymerase Chain Reaction ; Reproductive status ; Risk factors ; Science ; Sex hormones ; Signal transduction ; Structure-function relationships ; Studies ; Transmission electron microscopy ; Ultrastructure ; Weight reduction ; Western blotting</subject><ispartof>PloS one, 2015-09, Vol.10 (9), p.e0136421-e0136421</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Chen et al 2015 Chen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ddd635b5bae14d5de46de6aff1326dbb6458632db4e2ce37b92d7741f27181ba3</citedby><cites>FETCH-LOGICAL-c692t-ddd635b5bae14d5de46de6aff1326dbb6458632db4e2ce37b92d7741f27181ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556514/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556514/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26327438$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhang, Baohong</contributor><creatorcontrib>Chen, Wenqi</creatorcontrib><creatorcontrib>Xu, Xiaoyan</creatorcontrib><creatorcontrib>Wang, Lingjuan</creatorcontrib><creatorcontrib>Bai, Ge</creatorcontrib><creatorcontrib>Xiang, Wenpei</creatorcontrib><title>Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>This study aimed to construct a working model for detecting the mitochondrial damage and expression of Mfn2. It furthermore explored the pathogenesis of premature ovarian failure (POF) induced by cisplatin.
Forty young female mice were divided randomly into two groups. The first was the treatment group intraperitoneally administered cisplatin (1.5mg/kg). The untreated control group was likewise injected with physiological saline for 10 days. One month later, we observed the ovarian weight and morphological changes, particularly the development of follicles and concentration of sex hormones. Immunohistochemistry and western blotting were used to measure the two groups. We later evaluated ovarian cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels. We used transmission electron microscopy in order to observe the ultrastructure of ovarian cells. The phosphomolybdic acid colorimetric method was used to measure the ATP content in the ovarian tissue. Finally, the mitochondrial membrane potential of ovarian cells was detected with JC-1 dye.
The cisplatin resulted in a decline of body weight, reduced ovarian weight significantly, and resulted in disorders of the extrous cycle. The follicles' number decreased within the tissue's stromal hyperplasia. Moreover, E2 levels were reduced, and elevated gonadotropin levels were observed. However, Mfn2 was present in the cell's cytoplasm in both groups. Nevertheless, the Mfn2 levels and the expression of Bcl-2 were significantly decreased (p<0.05), but the expression of Bax and the apoptosis index (AI) was increased. In addition, the ATP levels (35.2 ± 5.7 μmol/g) of the control group were significantly higher (13.5 ± 3.8 μmol/g). Lastly, an obvious impairment of mitochondrial function and structure was observed.
The intreperitoneal injection of cisplatin, when administered for 10 days, establishes a POF model. Thus, the above results suggest that lower expression of Mfn2 may be involved in the mechanism of premature ovarian failure by affecting both the mitochondria's energy metabolism and its apoptosis. This decides the termination of the follicles' development.</description><subject>Animal tissues</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>ATP</subject><subject>Bax protein</subject><subject>Bcl-2 protein</subject><subject>Body weight</subject><subject>Cell cycle</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Colorimetry</subject><subject>Cytoplasm</subject><subject>Damage detection</subject><subject>Disease Models, Animal</subject><subject>Electron microscopy</subject><subject>Embryos</subject><subject>Endoplasmic reticulum</subject><subject>Energy metabolism</subject><subject>Failure</subject><subject>Family planning</subject><subject>Female</subject><subject>Follicles</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Gonadotropins</subject><subject>GTP Phosphohydrolases - deficiency</subject><subject>GTP Phosphohydrolases - physiology</subject><subject>Health aspects</subject><subject>Hormones</subject><subject>Hyperplasia</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial - physiology</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Microscopy, Electron, Transmission</subject><subject>Mitochondria</subject><subject>Mitochondria - physiology</subject><subject>Mitochondrial DNA</subject><subject>Ovarian diseases</subject><subject>Ovary - metabolism</subject><subject>Ovary - physiopathology</subject><subject>Ovary - ultrastructure</subject><subject>Pathogenesis</subject><subject>Phosphomolybdic acid</subject><subject>Pituitary (anterior)</subject><subject>Primary Ovarian Insufficiency - chemically induced</subject><subject>Primary Ovarian Insufficiency - physiopathology</subject><subject>Properties</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reproductive status</subject><subject>Risk factors</subject><subject>Science</subject><subject>Sex hormones</subject><subject>Signal transduction</subject><subject>Structure-function relationships</subject><subject>Studies</subject><subject>Transmission electron microscopy</subject><subject>Ultrastructure</subject><subject>Weight reduction</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99u0zAUxiMEYmPwBggsISG4aPG_OMkNUjU2qNSqCAa3lhOftK7SuNjONl6A58ZZs6pFu0C5cGz_vu_4HPskyUuCx4Rl5MPadq5VzXhrWxhjwgSn5FFySgpGR4Ji9vjg_yR55v0a45TlQjxNTqhgNOMsP03-zOwNurjdOvDe2BbZGs3rlqKpRxPvbWVUAI1uTFihuQm2WtlWO6Ma9Elt1BKQajWabO02WG98r15cq7jfoivjfQcemRaFFaCvDjYqdA72wKUyTT-fWw3N8-RJrRoPL4bxLPlxeXF1_mU0W3yenk9mo0oUNIy01oKlZVoqIFynGrjQIFRdE0aFLkvB0zympksOtAKWlQXVWcZJTTOSk1Kxs-T1znfbWC-HEnpJMpwXNOUsi8R0R2ir1nLrzEa539IqI-8WrFtK5YKpGpB1lUeB4KTAdTwILTMsygqwFqUuc0Wi18chWlduQFfQBqeaI9Pjndas5NJeS56mIiU8GrwbDJz9FasZ5Mb4CppGtWC7u3MXrEhx0cd68w_6cHYDtVQxAdPWNsatelM54TQTlBGMIzV-gIqfho2p4nurTVw_Erw_EkQmwG1Yqs57Of3-7f_Zxc9j9u0BuwLVhJW3TRfiU_XHIN-BlbPeO6j3RSZY9u1yXw3Zt4sc2iXKXh1e0F503x_sLz9rEJ4</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Chen, Wenqi</creator><creator>Xu, Xiaoyan</creator><creator>Wang, Lingjuan</creator><creator>Bai, Ge</creator><creator>Xiang, Wenpei</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150901</creationdate><title>Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model</title><author>Chen, Wenqi ; Xu, Xiaoyan ; Wang, Lingjuan ; Bai, Ge ; Xiang, Wenpei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-ddd635b5bae14d5de46de6aff1326dbb6458632db4e2ce37b92d7741f27181ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animal tissues</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>ATP</topic><topic>Bax protein</topic><topic>Bcl-2 protein</topic><topic>Body weight</topic><topic>Cell cycle</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Colorimetry</topic><topic>Cytoplasm</topic><topic>Damage detection</topic><topic>Disease Models, Animal</topic><topic>Electron microscopy</topic><topic>Embryos</topic><topic>Endoplasmic reticulum</topic><topic>Energy metabolism</topic><topic>Failure</topic><topic>Family planning</topic><topic>Female</topic><topic>Follicles</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Gonadotropins</topic><topic>GTP Phosphohydrolases - deficiency</topic><topic>GTP Phosphohydrolases - physiology</topic><topic>Health aspects</topic><topic>Hormones</topic><topic>Hyperplasia</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Membrane potential</topic><topic>Membrane Potential, Mitochondrial - physiology</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Microscopy, Electron, Transmission</topic><topic>Mitochondria</topic><topic>Mitochondria - physiology</topic><topic>Mitochondrial DNA</topic><topic>Ovarian diseases</topic><topic>Ovary - metabolism</topic><topic>Ovary - physiopathology</topic><topic>Ovary - ultrastructure</topic><topic>Pathogenesis</topic><topic>Phosphomolybdic acid</topic><topic>Pituitary (anterior)</topic><topic>Primary Ovarian Insufficiency - chemically induced</topic><topic>Primary Ovarian Insufficiency - physiopathology</topic><topic>Properties</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reproductive status</topic><topic>Risk factors</topic><topic>Science</topic><topic>Sex hormones</topic><topic>Signal transduction</topic><topic>Structure-function relationships</topic><topic>Studies</topic><topic>Transmission electron microscopy</topic><topic>Ultrastructure</topic><topic>Weight reduction</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Wenqi</creatorcontrib><creatorcontrib>Xu, Xiaoyan</creatorcontrib><creatorcontrib>Wang, Lingjuan</creatorcontrib><creatorcontrib>Bai, Ge</creatorcontrib><creatorcontrib>Xiang, Wenpei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Wenqi</au><au>Xu, Xiaoyan</au><au>Wang, Lingjuan</au><au>Bai, Ge</au><au>Xiang, Wenpei</au><au>Zhang, Baohong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>10</volume><issue>9</issue><spage>e0136421</spage><epage>e0136421</epage><pages>e0136421-e0136421</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>This study aimed to construct a working model for detecting the mitochondrial damage and expression of Mfn2. It furthermore explored the pathogenesis of premature ovarian failure (POF) induced by cisplatin.
Forty young female mice were divided randomly into two groups. The first was the treatment group intraperitoneally administered cisplatin (1.5mg/kg). The untreated control group was likewise injected with physiological saline for 10 days. One month later, we observed the ovarian weight and morphological changes, particularly the development of follicles and concentration of sex hormones. Immunohistochemistry and western blotting were used to measure the two groups. We later evaluated ovarian cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels. We used transmission electron microscopy in order to observe the ultrastructure of ovarian cells. The phosphomolybdic acid colorimetric method was used to measure the ATP content in the ovarian tissue. Finally, the mitochondrial membrane potential of ovarian cells was detected with JC-1 dye.
The cisplatin resulted in a decline of body weight, reduced ovarian weight significantly, and resulted in disorders of the extrous cycle. The follicles' number decreased within the tissue's stromal hyperplasia. Moreover, E2 levels were reduced, and elevated gonadotropin levels were observed. However, Mfn2 was present in the cell's cytoplasm in both groups. Nevertheless, the Mfn2 levels and the expression of Bcl-2 were significantly decreased (p<0.05), but the expression of Bax and the apoptosis index (AI) was increased. In addition, the ATP levels (35.2 ± 5.7 μmol/g) of the control group were significantly higher (13.5 ± 3.8 μmol/g). Lastly, an obvious impairment of mitochondrial function and structure was observed.
The intreperitoneal injection of cisplatin, when administered for 10 days, establishes a POF model. Thus, the above results suggest that lower expression of Mfn2 may be involved in the mechanism of premature ovarian failure by affecting both the mitochondria's energy metabolism and its apoptosis. This decides the termination of the follicles' development.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26327438</pmid><doi>10.1371/journal.pone.0136421</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1708925437 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animal tissues Animals Apoptosis Apoptosis - physiology ATP Bax protein Bcl-2 protein Body weight Cell cycle Cisplatin Cisplatin - pharmacology Colorimetry Cytoplasm Damage detection Disease Models, Animal Electron microscopy Embryos Endoplasmic reticulum Energy metabolism Failure Family planning Female Follicles Gene expression Genetic aspects Gonadotropins GTP Phosphohydrolases - deficiency GTP Phosphohydrolases - physiology Health aspects Hormones Hyperplasia Immunohistochemistry In Situ Nick-End Labeling Membrane potential Membrane Potential, Mitochondrial - physiology Metabolism Mice Microscopy, Electron, Transmission Mitochondria Mitochondria - physiology Mitochondrial DNA Ovarian diseases Ovary - metabolism Ovary - physiopathology Ovary - ultrastructure Pathogenesis Phosphomolybdic acid Pituitary (anterior) Primary Ovarian Insufficiency - chemically induced Primary Ovarian Insufficiency - physiopathology Properties Real-Time Polymerase Chain Reaction Reproductive status Risk factors Science Sex hormones Signal transduction Structure-function relationships Studies Transmission electron microscopy Ultrastructure Weight reduction Western blotting |
| title | Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T00%3A04%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Low%20Expression%20of%20Mfn2%20Is%20Associated%20with%20Mitochondrial%20Damage%20and%20Apoptosis%20of%20Ovarian%20Tissues%20in%20the%20Premature%20Ovarian%20Failure%20Model&rft.jtitle=PloS%20one&rft.au=Chen,%20Wenqi&rft.date=2015-09-01&rft.volume=10&rft.issue=9&rft.spage=e0136421&rft.epage=e0136421&rft.pages=e0136421-e0136421&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0136421&rft_dat=%3Cgale_plos_%3EA427623100%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1708925437&rft_id=info:pmid/26327438&rft_galeid=A427623100&rft_doaj_id=oai_doaj_org_article_fc837364190f46d2b706bce0d6bdb8a1&rfr_iscdi=true |