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
Hauptverfasser: 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
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container_end_page 388
container_issue 2
container_start_page 384
container_title Fertility and sterility
container_volume 96
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. 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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><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. 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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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source MEDLINE; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
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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