The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation
Objective To determine the impact of reproductive aging on oocyte mitochondrial quantity, function, and DNA (mtDNA) integrity. Design Prospective observational study. Setting IVF clinic in a tertiary academic care center. Patient(s) One hundred two oocytes from 32 women undergoing IVF. Intervention(...
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Veröffentlicht in: | Fertility and sterility 2011-08, Vol.96 (2), p.384-388 |
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creator | Duran, Hakan E., M.D Simsek-Duran, Fatma, M.D Oehninger, Sergio C., M.D., Ph.D Jones, Howard W., M.D Castora, Frank J., Ph.D |
description | Objective To determine the impact of reproductive aging on oocyte mitochondrial quantity, function, and DNA (mtDNA) integrity. Design Prospective observational study. Setting IVF clinic in a tertiary academic care center. Patient(s) One hundred two oocytes from 32 women undergoing IVF. Intervention(s) None. Main Outcome Measure(s) Adenosine triphosphate (ATP) levels, mtDNA number, and mtDNA deletion occurrence in individual oocytes. Result(s) Oocyte ATP content increases with maturation (786 ± 87 fmol, 1,037 ± 57 fmol, and 1,201 ± 59 fmol for prophase 1 [P1], metaphase 1 [M1], and metaphase 2 [M2] oocytes, respectively), whereas mtDNA copy numbers do not change (64,500 ± 20,440, 180,000 ± 44,040, and 143,000 ± 31,210 for P1, M1, and M2 oocytes, respectively). Stepwise multiple regression analysis identified developmental stage as a determinant of oocyte ATP, whereas number of oocytes retrieved and cycle day 3 FSH level were determinants of mtDNA copy number. Of the 15 oocytes found to possess the 5-kb mtDNA deletion, 10 were arrested or degenerated oocytes. Conclusion(s) Although no direct association was found between female age and oocyte mitochondrial quantity and function, the number of mitochondria was predicted by ovarian reserve indicators. As the oocyte matures, ATP content increases. |
doi_str_mv | 10.1016/j.fertnstert.2011.05.056 |
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Design Prospective observational study. Setting IVF clinic in a tertiary academic care center. Patient(s) One hundred two oocytes from 32 women undergoing IVF. Intervention(s) None. Main Outcome Measure(s) Adenosine triphosphate (ATP) levels, mtDNA number, and mtDNA deletion occurrence in individual oocytes. Result(s) Oocyte ATP content increases with maturation (786 ± 87 fmol, 1,037 ± 57 fmol, and 1,201 ± 59 fmol for prophase 1 [P1], metaphase 1 [M1], and metaphase 2 [M2] oocytes, respectively), whereas mtDNA copy numbers do not change (64,500 ± 20,440, 180,000 ± 44,040, and 143,000 ± 31,210 for P1, M1, and M2 oocytes, respectively). Stepwise multiple regression analysis identified developmental stage as a determinant of oocyte ATP, whereas number of oocytes retrieved and cycle day 3 FSH level were determinants of mtDNA copy number. Of the 15 oocytes found to possess the 5-kb mtDNA deletion, 10 were arrested or degenerated oocytes. Conclusion(s) Although no direct association was found between female age and oocyte mitochondrial quantity and function, the number of mitochondria was predicted by ovarian reserve indicators. As the oocyte matures, ATP content increases.</description><identifier>ISSN: 0015-0282</identifier><identifier>EISSN: 1556-5653</identifier><identifier>DOI: 10.1016/j.fertnstert.2011.05.056</identifier><identifier>PMID: 21683351</identifier><identifier>CODEN: FESTAS</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Academic Medical Centers ; adenosine triphosphate ; Adenosine Triphosphate - metabolism ; Adult ; Age Factors ; aging ; Aging - genetics ; Aging - pathology ; Analysis of Variance ; ATP content ; Biological and medical sciences ; Cells, Cultured ; Cellular Senescence - genetics ; common deletion ; developmental stages ; DNA Damage ; DNA, Mitochondrial - metabolism ; Female ; Fertilization in Vitro ; follicle-stimulating hormone ; FSH ; Gynecology. Andrology. Obstetrics ; human oocytes ; Humans ; in vitro fertilization ; Internal Medicine ; Logistic Models ; Medical sciences ; Meiotic Prophase I ; Metaphase ; metaphase 2 ; mitochondria ; Mitochondria - metabolism ; Mitochondria - pathology ; Mitochondrial DNA ; observational studies ; Obstetrics and Gynecology ; Oocyte Retrieval ; oocytes ; Oocytes - metabolism ; Oocytes - pathology ; Ovulation Induction ; patients ; prophase ; Prospective Studies ; regression analysis ; Reproduction - genetics ; senescence ; Virginia ; women ; Young Adult</subject><ispartof>Fertility and sterility, 2011-08, Vol.96 (2), p.384-388</ispartof><rights>American Society for Reproductive Medicine</rights><rights>2011 American Society for Reproductive Medicine</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-8312f12be3befdbac1e3c7becb26e4538524b98b58da01ccb98b595d2d24dc553</citedby><cites>FETCH-LOGICAL-c532t-8312f12be3befdbac1e3c7becb26e4538524b98b58da01ccb98b595d2d24dc553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.fertnstert.2011.05.056$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24412066$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21683351$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Duran, Hakan E., M.D</creatorcontrib><creatorcontrib>Simsek-Duran, Fatma, M.D</creatorcontrib><creatorcontrib>Oehninger, Sergio C., M.D., Ph.D</creatorcontrib><creatorcontrib>Jones, Howard W., M.D</creatorcontrib><creatorcontrib>Castora, Frank J., Ph.D</creatorcontrib><title>The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation</title><title>Fertility and sterility</title><addtitle>Fertil Steril</addtitle><description>Objective To determine the impact of reproductive aging on oocyte mitochondrial quantity, function, and DNA (mtDNA) integrity. Design Prospective observational study. Setting IVF clinic in a tertiary academic care center. Patient(s) One hundred two oocytes from 32 women undergoing IVF. Intervention(s) None. Main Outcome Measure(s) Adenosine triphosphate (ATP) levels, mtDNA number, and mtDNA deletion occurrence in individual oocytes. Result(s) Oocyte ATP content increases with maturation (786 ± 87 fmol, 1,037 ± 57 fmol, and 1,201 ± 59 fmol for prophase 1 [P1], metaphase 1 [M1], and metaphase 2 [M2] oocytes, respectively), whereas mtDNA copy numbers do not change (64,500 ± 20,440, 180,000 ± 44,040, and 143,000 ± 31,210 for P1, M1, and M2 oocytes, respectively). Stepwise multiple regression analysis identified developmental stage as a determinant of oocyte ATP, whereas number of oocytes retrieved and cycle day 3 FSH level were determinants of mtDNA copy number. Of the 15 oocytes found to possess the 5-kb mtDNA deletion, 10 were arrested or degenerated oocytes. Conclusion(s) Although no direct association was found between female age and oocyte mitochondrial quantity and function, the number of mitochondria was predicted by ovarian reserve indicators. As the oocyte matures, ATP content increases.</description><subject>Academic Medical Centers</subject><subject>adenosine triphosphate</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Adult</subject><subject>Age Factors</subject><subject>aging</subject><subject>Aging - genetics</subject><subject>Aging - pathology</subject><subject>Analysis of Variance</subject><subject>ATP content</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Cellular Senescence - genetics</subject><subject>common deletion</subject><subject>developmental stages</subject><subject>DNA Damage</subject><subject>DNA, Mitochondrial - metabolism</subject><subject>Female</subject><subject>Fertilization in Vitro</subject><subject>follicle-stimulating hormone</subject><subject>FSH</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>human oocytes</subject><subject>Humans</subject><subject>in vitro fertilization</subject><subject>Internal Medicine</subject><subject>Logistic Models</subject><subject>Medical sciences</subject><subject>Meiotic Prophase I</subject><subject>Metaphase</subject><subject>metaphase 2</subject><subject>mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Mitochondrial DNA</subject><subject>observational studies</subject><subject>Obstetrics and Gynecology</subject><subject>Oocyte Retrieval</subject><subject>oocytes</subject><subject>Oocytes - metabolism</subject><subject>Oocytes - pathology</subject><subject>Ovulation Induction</subject><subject>patients</subject><subject>prophase</subject><subject>Prospective Studies</subject><subject>regression analysis</subject><subject>Reproduction - genetics</subject><subject>senescence</subject><subject>Virginia</subject><subject>women</subject><subject>Young Adult</subject><issn>0015-0282</issn><issn>1556-5653</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUsluFDEQbSEQGQK_AL4gLunBS7uXC1IIqxTBIcnZctvVGQ_ddmK7g-ZH-F6qMwOROCGV7JL96tXyqigIo2tGWf12ux4gZp8ynmtOGVtTiVY_KlZMyrqUtRSPixWlTJaUt_yoeJbSllJas4Y_LY44q1shJFsVvy43QHRKwTidXfAkDCTCTQx2NtndAUngIRnwBshPlzdkcjmYTfA2Oj2S21n77PLuhAyzNwvBCdHekg_fTonzGa4jfqJHNvOkkTyYXYZEdCbWDdgD-ExS1tf4hoknned4X8bz4smgxwQvDvdxcfXp4-XZl_L8--evZ6fnpZGC57IVjA-M9yB6GGyvDQNhmh5Mz2uopGglr_qu7WVrNWXG3PudtNzyyhopxXHxZs-LHd_OkLKaHHY7jtpDmJNqmw4H3kmByHaPNDGkFGFQN9FNOu4Uo2oRRW3VgyhqEUVRiVZj6MtDkrmfwP4N_KMCAl4fADoZPQ5Re-PSA66qGKf1QvRqjxt0UBpnm9TVBWaSKDRvum5her9HAA7tzkFUybhFPOsimKxscP9T77t_SMzovMPKfsAO0jbM0aMoiqnEFVUXy5otW8YYpW3FGvEb09LSjQ</recordid><startdate>20110801</startdate><enddate>20110801</enddate><creator>Duran, Hakan E., M.D</creator><creator>Simsek-Duran, Fatma, M.D</creator><creator>Oehninger, Sergio C., M.D., Ph.D</creator><creator>Jones, Howard W., M.D</creator><creator>Castora, Frank J., Ph.D</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>FBQ</scope><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>20110801</creationdate><title>The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation</title><author>Duran, Hakan E., M.D ; Simsek-Duran, Fatma, M.D ; Oehninger, Sergio C., M.D., Ph.D ; Jones, Howard W., M.D ; Castora, Frank J., Ph.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-8312f12be3befdbac1e3c7becb26e4538524b98b58da01ccb98b595d2d24dc553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Academic Medical Centers</topic><topic>adenosine triphosphate</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Adult</topic><topic>Age Factors</topic><topic>aging</topic><topic>Aging - genetics</topic><topic>Aging - pathology</topic><topic>Analysis of Variance</topic><topic>ATP content</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Cellular Senescence - genetics</topic><topic>common deletion</topic><topic>developmental stages</topic><topic>DNA Damage</topic><topic>DNA, Mitochondrial - metabolism</topic><topic>Female</topic><topic>Fertilization in Vitro</topic><topic>follicle-stimulating hormone</topic><topic>FSH</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>human oocytes</topic><topic>Humans</topic><topic>in vitro fertilization</topic><topic>Internal Medicine</topic><topic>Logistic Models</topic><topic>Medical sciences</topic><topic>Meiotic Prophase I</topic><topic>Metaphase</topic><topic>metaphase 2</topic><topic>mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - pathology</topic><topic>Mitochondrial DNA</topic><topic>observational studies</topic><topic>Obstetrics and Gynecology</topic><topic>Oocyte Retrieval</topic><topic>oocytes</topic><topic>Oocytes - metabolism</topic><topic>Oocytes - pathology</topic><topic>Ovulation Induction</topic><topic>patients</topic><topic>prophase</topic><topic>Prospective Studies</topic><topic>regression analysis</topic><topic>Reproduction - genetics</topic><topic>senescence</topic><topic>Virginia</topic><topic>women</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duran, Hakan E., M.D</creatorcontrib><creatorcontrib>Simsek-Duran, Fatma, M.D</creatorcontrib><creatorcontrib>Oehninger, Sergio C., M.D., Ph.D</creatorcontrib><creatorcontrib>Jones, Howard W., M.D</creatorcontrib><creatorcontrib>Castora, Frank J., Ph.D</creatorcontrib><collection>AGRIS</collection><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>Fertility and sterility</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duran, Hakan E., M.D</au><au>Simsek-Duran, Fatma, M.D</au><au>Oehninger, Sergio C., M.D., Ph.D</au><au>Jones, Howard W., M.D</au><au>Castora, Frank J., Ph.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation</atitle><jtitle>Fertility and sterility</jtitle><addtitle>Fertil Steril</addtitle><date>2011-08-01</date><risdate>2011</risdate><volume>96</volume><issue>2</issue><spage>384</spage><epage>388</epage><pages>384-388</pages><issn>0015-0282</issn><eissn>1556-5653</eissn><coden>FESTAS</coden><abstract>Objective To determine the impact of reproductive aging on oocyte mitochondrial quantity, function, and DNA (mtDNA) integrity. Design Prospective observational study. Setting IVF clinic in a tertiary academic care center. Patient(s) One hundred two oocytes from 32 women undergoing IVF. Intervention(s) None. Main Outcome Measure(s) Adenosine triphosphate (ATP) levels, mtDNA number, and mtDNA deletion occurrence in individual oocytes. Result(s) Oocyte ATP content increases with maturation (786 ± 87 fmol, 1,037 ± 57 fmol, and 1,201 ± 59 fmol for prophase 1 [P1], metaphase 1 [M1], and metaphase 2 [M2] oocytes, respectively), whereas mtDNA copy numbers do not change (64,500 ± 20,440, 180,000 ± 44,040, and 143,000 ± 31,210 for P1, M1, and M2 oocytes, respectively). Stepwise multiple regression analysis identified developmental stage as a determinant of oocyte ATP, whereas number of oocytes retrieved and cycle day 3 FSH level were determinants of mtDNA copy number. Of the 15 oocytes found to possess the 5-kb mtDNA deletion, 10 were arrested or degenerated oocytes. Conclusion(s) Although no direct association was found between female age and oocyte mitochondrial quantity and function, the number of mitochondria was predicted by ovarian reserve indicators. As the oocyte matures, ATP content increases.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>21683351</pmid><doi>10.1016/j.fertnstert.2011.05.056</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Academic Medical Centers adenosine triphosphate Adenosine Triphosphate - metabolism Adult Age Factors aging Aging - genetics Aging - pathology Analysis of Variance ATP content Biological and medical sciences Cells, Cultured Cellular Senescence - genetics common deletion developmental stages DNA Damage DNA, Mitochondrial - metabolism Female Fertilization in Vitro follicle-stimulating hormone FSH Gynecology. Andrology. Obstetrics human oocytes Humans in vitro fertilization Internal Medicine Logistic Models Medical sciences Meiotic Prophase I Metaphase metaphase 2 mitochondria Mitochondria - metabolism Mitochondria - pathology Mitochondrial DNA observational studies Obstetrics and Gynecology Oocyte Retrieval oocytes Oocytes - metabolism Oocytes - pathology Ovulation Induction patients prophase Prospective Studies regression analysis Reproduction - genetics senescence Virginia women Young Adult |
title | The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation |
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