Low expression of Mfn2 is associated with mitochondrial damage and apoptosis in the placental villi of early unexplained miscarriage
Abstract Introduction Early miscarriage is the most common complication of pregnancy and in many cases the etiology is not clearly understood. We aim to profile the expression of Mfn2 and mitochondrial damage in villous tissues, in order to determine the underlying mechanism of unexplained miscarria...
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| Veröffentlicht in: | Placenta (Eastbourne) 2013-07, Vol.34 (7), p.613-618 |
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| creator | Pang, W Zhang, Y Zhao, N Darwiche, S.S Fu, X Xiang, W |
| description | Abstract Introduction Early miscarriage is the most common complication of pregnancy and in many cases the etiology is not clearly understood. We aim to profile the expression of Mfn2 and mitochondrial damage in villous tissues, in order to determine the underlying mechanism of unexplained miscarriage. Methods We investigated placental villous samples of 30 women with early unexplained miscarriage (miscarriage group) and 30 women with normal pregnancy (control group). Immunohistochemistry and western blotting were used to detect the Mfn2 expression. We observed trophoblastic cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels by western blotting. Transmission electron microscopy was used to analyze mitochondrial morphology and phosphomolybdic acid colorimetric method was used to measure the ATP content of all villous samples. Results Mfn2 staining showed extra-nuclear localization in the trophoblastic cells. Compared with the control group, the levels of Mfn2 and Bcl-2 were markedly decreased ( P |
| doi_str_mv | 10.1016/j.placenta.2013.03.013 |
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We aim to profile the expression of Mfn2 and mitochondrial damage in villous tissues, in order to determine the underlying mechanism of unexplained miscarriage. Methods We investigated placental villous samples of 30 women with early unexplained miscarriage (miscarriage group) and 30 women with normal pregnancy (control group). Immunohistochemistry and western blotting were used to detect the Mfn2 expression. We observed trophoblastic cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels by western blotting. Transmission electron microscopy was used to analyze mitochondrial morphology and phosphomolybdic acid colorimetric method was used to measure the ATP content of all villous samples. Results Mfn2 staining showed extra-nuclear localization in the trophoblastic cells. Compared with the control group, the levels of Mfn2 and Bcl-2 were markedly decreased ( P < 0.01), while both the levels of Bax protein and apoptosis index (AI) were increased in the miscarriage group ( P < 0.01). Mfn2 levels positively correlated with Bcl-2, but negatively correlated with Bax. Moreover, compared to the control group (33.8 ± 6.5 μmol/g), ATP levels in the miscarriage group were significantly decreased (15.8 ± 4.8 μmol/g). In addition, obvious impairment of mitochondrial function was observed in trophoblastic cells from the unexplained miscarriage group. Conclusion Mitochondrial morphologic and functional changes were observed in trophoblastic cells, and in relation with apoptosis, may be correlated with low levels of Mfn2. Deficient expression of Mfn2 in trophoblastic cells could be an important cause of early miscarriage.</description><identifier>ISSN: 0143-4004</identifier><identifier>EISSN: 1532-3102</identifier><identifier>DOI: 10.1016/j.placenta.2013.03.013</identifier><identifier>PMID: 23601695</identifier><identifier>CODEN: PLACDF</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Abortion, Spontaneous - metabolism ; Abortion, Spontaneous - pathology ; Adenosine Triphosphate - biosynthesis ; Apoptosis ; bcl-2-Associated X Protein - metabolism ; Biological and medical sciences ; Chorionic Villi - pathology ; Embryology: invertebrates and vertebrates. Teratology ; Female ; Fundamental and applied biological sciences. Psychology ; GTP Phosphohydrolases - biosynthesis ; Humans ; Internal Medicine ; Miscarriage ; Mitochondria ; Mitochondria - metabolism ; Mitochondria - pathology ; Mitochondrial Proteins - biosynthesis ; Mitofusin 2 ; Obstetrics and Gynecology ; Placental villous ; Pregnancy ; Pregnancy. Parturition. Lactation ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Trophoblasts - pathology ; Vertebrates: reproduction</subject><ispartof>Placenta (Eastbourne), 2013-07, Vol.34 (7), p.613-618</ispartof><rights>Elsevier Ltd</rights><rights>2013 Elsevier Ltd</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-ba8c068bd78e5f5ad122cd90206fbb4378f20e321c10f535c2d256ddd8386e73</citedby><cites>FETCH-LOGICAL-c453t-ba8c068bd78e5f5ad122cd90206fbb4378f20e321c10f535c2d256ddd8386e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.placenta.2013.03.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27433714$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23601695$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pang, W</creatorcontrib><creatorcontrib>Zhang, Y</creatorcontrib><creatorcontrib>Zhao, N</creatorcontrib><creatorcontrib>Darwiche, S.S</creatorcontrib><creatorcontrib>Fu, X</creatorcontrib><creatorcontrib>Xiang, W</creatorcontrib><title>Low expression of Mfn2 is associated with mitochondrial damage and apoptosis in the placental villi of early unexplained miscarriage</title><title>Placenta (Eastbourne)</title><addtitle>Placenta</addtitle><description>Abstract Introduction Early miscarriage is the most common complication of pregnancy and in many cases the etiology is not clearly understood. We aim to profile the expression of Mfn2 and mitochondrial damage in villous tissues, in order to determine the underlying mechanism of unexplained miscarriage. Methods We investigated placental villous samples of 30 women with early unexplained miscarriage (miscarriage group) and 30 women with normal pregnancy (control group). Immunohistochemistry and western blotting were used to detect the Mfn2 expression. We observed trophoblastic cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels by western blotting. Transmission electron microscopy was used to analyze mitochondrial morphology and phosphomolybdic acid colorimetric method was used to measure the ATP content of all villous samples. Results Mfn2 staining showed extra-nuclear localization in the trophoblastic cells. Compared with the control group, the levels of Mfn2 and Bcl-2 were markedly decreased ( P < 0.01), while both the levels of Bax protein and apoptosis index (AI) were increased in the miscarriage group ( P < 0.01). Mfn2 levels positively correlated with Bcl-2, but negatively correlated with Bax. Moreover, compared to the control group (33.8 ± 6.5 μmol/g), ATP levels in the miscarriage group were significantly decreased (15.8 ± 4.8 μmol/g). In addition, obvious impairment of mitochondrial function was observed in trophoblastic cells from the unexplained miscarriage group. Conclusion Mitochondrial morphologic and functional changes were observed in trophoblastic cells, and in relation with apoptosis, may be correlated with low levels of Mfn2. Deficient expression of Mfn2 in trophoblastic cells could be an important cause of early miscarriage.</description><subject>Abortion, Spontaneous - metabolism</subject><subject>Abortion, Spontaneous - pathology</subject><subject>Adenosine Triphosphate - biosynthesis</subject><subject>Apoptosis</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biological and medical sciences</subject><subject>Chorionic Villi - pathology</subject><subject>Embryology: invertebrates and vertebrates. Teratology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>GTP Phosphohydrolases - biosynthesis</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Miscarriage</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Mitochondrial Proteins - biosynthesis</subject><subject>Mitofusin 2</subject><subject>Obstetrics and Gynecology</subject><subject>Placental villous</subject><subject>Pregnancy</subject><subject>Pregnancy. Parturition. Lactation</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Trophoblasts - pathology</subject><subject>Vertebrates: reproduction</subject><issn>0143-4004</issn><issn>1532-3102</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2PEzEMhiMEYkvhL6xyQeLS4iSTmekFgVZ8SUUc2HuUJp5tSiYZkpldeueHk1FbkLggWfLl9WP7tQm5ZrBmwOrXh_XgtcEw6jUHJtZQgolHZMGk4CvBgD8mC2CVWFUA1RV5lvMBADYV40_JFRd1gWzkgvzaxgeKP4eEObsYaOzoly5w6jLVOUfj9IiWPrhxT3s3RrOPwSanPbW613dIdbBUD3EYYy4lLtBxj_Qymqf3zns3Q1Enf6RTKK28dqEwe5eNToV1h8_Jk077jC_OeUluP7y_vfm02n79-Pnm3XZlKinG1U63Bup2Z5sWZSe1ZZwbuwEOdbfbVaJpOw4oODMMOimk4ZbL2lrbirbGRizJqxN2SPHHhHlU8wzovQ4Yp6yYqCXI2ZkirU9Sk2LOCTs1JNfrdFQM1HwAdVCXLdV8AAUlmCiF1-ce065H-6fs4ngRvDwLdNnfd0kH4_JfXVMJ0ZS7Lcnbkw6LIfcOk8rGYTBoXUIzKhvd_2d58w_CeBdc6fodj5gPcUqh2K2YylyB-ja_y_wtTECh1lL8BjZ9viM</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Pang, W</creator><creator>Zhang, Y</creator><creator>Zhao, N</creator><creator>Darwiche, S.S</creator><creator>Fu, X</creator><creator>Xiang, W</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><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>20130701</creationdate><title>Low expression of Mfn2 is associated with mitochondrial damage and apoptosis in the placental villi of early unexplained miscarriage</title><author>Pang, W ; Zhang, Y ; Zhao, N ; Darwiche, S.S ; Fu, X ; Xiang, W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-ba8c068bd78e5f5ad122cd90206fbb4378f20e321c10f535c2d256ddd8386e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Abortion, Spontaneous - metabolism</topic><topic>Abortion, Spontaneous - pathology</topic><topic>Adenosine Triphosphate - biosynthesis</topic><topic>Apoptosis</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Biological and medical sciences</topic><topic>Chorionic Villi - pathology</topic><topic>Embryology: invertebrates and vertebrates. Teratology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>GTP Phosphohydrolases - biosynthesis</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Miscarriage</topic><topic>Mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - pathology</topic><topic>Mitochondrial Proteins - biosynthesis</topic><topic>Mitofusin 2</topic><topic>Obstetrics and Gynecology</topic><topic>Placental villous</topic><topic>Pregnancy</topic><topic>Pregnancy. Parturition. Lactation</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Trophoblasts - pathology</topic><topic>Vertebrates: reproduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pang, W</creatorcontrib><creatorcontrib>Zhang, Y</creatorcontrib><creatorcontrib>Zhao, N</creatorcontrib><creatorcontrib>Darwiche, S.S</creatorcontrib><creatorcontrib>Fu, X</creatorcontrib><creatorcontrib>Xiang, W</creatorcontrib><collection>Pascal-Francis</collection><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>Placenta (Eastbourne)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pang, W</au><au>Zhang, Y</au><au>Zhao, N</au><au>Darwiche, S.S</au><au>Fu, X</au><au>Xiang, W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low expression of Mfn2 is associated with mitochondrial damage and apoptosis in the placental villi of early unexplained miscarriage</atitle><jtitle>Placenta (Eastbourne)</jtitle><addtitle>Placenta</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>34</volume><issue>7</issue><spage>613</spage><epage>618</epage><pages>613-618</pages><issn>0143-4004</issn><eissn>1532-3102</eissn><coden>PLACDF</coden><abstract>Abstract Introduction Early miscarriage is the most common complication of pregnancy and in many cases the etiology is not clearly understood. We aim to profile the expression of Mfn2 and mitochondrial damage in villous tissues, in order to determine the underlying mechanism of unexplained miscarriage. Methods We investigated placental villous samples of 30 women with early unexplained miscarriage (miscarriage group) and 30 women with normal pregnancy (control group). Immunohistochemistry and western blotting were used to detect the Mfn2 expression. We observed trophoblastic cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels by western blotting. Transmission electron microscopy was used to analyze mitochondrial morphology and phosphomolybdic acid colorimetric method was used to measure the ATP content of all villous samples. Results Mfn2 staining showed extra-nuclear localization in the trophoblastic cells. Compared with the control group, the levels of Mfn2 and Bcl-2 were markedly decreased ( P < 0.01), while both the levels of Bax protein and apoptosis index (AI) were increased in the miscarriage group ( P < 0.01). Mfn2 levels positively correlated with Bcl-2, but negatively correlated with Bax. Moreover, compared to the control group (33.8 ± 6.5 μmol/g), ATP levels in the miscarriage group were significantly decreased (15.8 ± 4.8 μmol/g). In addition, obvious impairment of mitochondrial function was observed in trophoblastic cells from the unexplained miscarriage group. Conclusion Mitochondrial morphologic and functional changes were observed in trophoblastic cells, and in relation with apoptosis, may be correlated with low levels of Mfn2. Deficient expression of Mfn2 in trophoblastic cells could be an important cause of early miscarriage.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>23601695</pmid><doi>10.1016/j.placenta.2013.03.013</doi><tpages>6</tpages></addata></record> |
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| subjects | Abortion, Spontaneous - metabolism Abortion, Spontaneous - pathology Adenosine Triphosphate - biosynthesis Apoptosis bcl-2-Associated X Protein - metabolism Biological and medical sciences Chorionic Villi - pathology Embryology: invertebrates and vertebrates. Teratology Female Fundamental and applied biological sciences. Psychology GTP Phosphohydrolases - biosynthesis Humans Internal Medicine Miscarriage Mitochondria Mitochondria - metabolism Mitochondria - pathology Mitochondrial Proteins - biosynthesis Mitofusin 2 Obstetrics and Gynecology Placental villous Pregnancy Pregnancy. Parturition. Lactation Proto-Oncogene Proteins c-bcl-2 - metabolism Trophoblasts - pathology Vertebrates: reproduction |
| title | Low expression of Mfn2 is associated with mitochondrial damage and apoptosis in the placental villi of early unexplained miscarriage |
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