Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared with Moderate-Weight Women

Context: Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period. Objective: This study sought to determine whether there are alterations in the preovulatory follicular en...

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Veröffentlicht in:The journal of clinical endocrinology and metabolism 2009-05, Vol.94 (5), p.1533-1540
Hauptverfasser: Robker, Rebecca L., Akison, Lisa K., Bennett, Brenton D., Thrupp, Penny N., Chura, Lindsay R., Russell, Darryl L., Lane, Michelle, Norman, Robert J.
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container_end_page 1540
container_issue 5
container_start_page 1533
container_title The journal of clinical endocrinology and metabolism
container_volume 94
creator Robker, Rebecca L.
Akison, Lisa K.
Bennett, Brenton D.
Thrupp, Penny N.
Chura, Lindsay R.
Russell, Darryl L.
Lane, Michelle
Norman, Robert J.
description Context: Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period. Objective: This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence. Design, Setting, and Participants: Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33; BMI 20–24.9 kg/m2), overweight (n = 31; BMI 25–29.9 kg/m2), and obese (n =32; BMI ≥30 kg/m2). Intervention: For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes. Main Outcome Measures: Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance. Results: Increasing BMI was associated with increased follicular fluid insulin (P < 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P < 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women. Conclusions: Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients. Increasing body mass index is associated with alterations in the ovarian follicular environment.
doi_str_mv 10.1210/jc.2008-2648
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Objective: This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence. Design, Setting, and Participants: Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33; BMI 20–24.9 kg/m2), overweight (n = 31; BMI 25–29.9 kg/m2), and obese (n =32; BMI ≥30 kg/m2). Intervention: For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes. Main Outcome Measures: Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance. Results: Increasing BMI was associated with increased follicular fluid insulin (P &lt; 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P &lt; 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women. Conclusions: Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients. 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Psychology ; Gene Expression - physiology ; Granulosa Cells - metabolism ; Hormones - biosynthesis ; Hormones - genetics ; Hormones - metabolism ; Humans ; Medical sciences ; Obesity - genetics ; Obesity - metabolism ; Oocytes - physiology ; Ovary - metabolism ; Reproduction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - biosynthesis ; RNA - isolation &amp; purification ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vertebrates: endocrinology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2009-05, Vol.94 (5), p.1533-1540</ispartof><rights>Copyright © 2009 by The Endocrine Society</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4083-5f799b6a2c1470d20292045c56c403abfbeab2d58fcc46b6d8888174893ed63</citedby><cites>FETCH-LOGICAL-c4083-5f799b6a2c1470d20292045c56c403abfbeab2d58fcc46b6d8888174893ed63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27913,27914</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=21525325$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19223519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Robker, Rebecca L.</creatorcontrib><creatorcontrib>Akison, Lisa K.</creatorcontrib><creatorcontrib>Bennett, Brenton D.</creatorcontrib><creatorcontrib>Thrupp, Penny N.</creatorcontrib><creatorcontrib>Chura, Lindsay R.</creatorcontrib><creatorcontrib>Russell, Darryl L.</creatorcontrib><creatorcontrib>Lane, Michelle</creatorcontrib><creatorcontrib>Norman, Robert J.</creatorcontrib><title>Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared with Moderate-Weight Women</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context: Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period. Objective: This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence. Design, Setting, and Participants: Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33; BMI 20–24.9 kg/m2), overweight (n = 31; BMI 25–29.9 kg/m2), and obese (n =32; BMI ≥30 kg/m2). Intervention: For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes. Main Outcome Measures: Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance. Results: Increasing BMI was associated with increased follicular fluid insulin (P &lt; 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P &lt; 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women. Conclusions: Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients. 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Psychology</subject><subject>Gene Expression - physiology</subject><subject>Granulosa Cells - metabolism</subject><subject>Hormones - biosynthesis</subject><subject>Hormones - genetics</subject><subject>Hormones - metabolism</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Obesity - genetics</subject><subject>Obesity - metabolism</subject><subject>Oocytes - physiology</subject><subject>Ovary - metabolism</subject><subject>Reproduction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - biosynthesis</subject><subject>RNA - isolation &amp; purification</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vertebrates: endocrinology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkUGP1CAUgInRuLOjN8-Gi562K1Boy9HMrrsmu5mDJuuNAH21jC2M0Druv1_GTvTiC-RB-N6DfCD0hpJLyij5sLOXjJCmYBVvnqEVlVwUNZX1c7QihNFC1uzbGTpPaUcI5VyUL9EZlYyVgsoVetwaSIAfwggeX__unXETvnJdBxG8hYSdx9tfOjrt8T1M2oTBTZAu8G2IY_DHlfYtvgEPuXwfISUXPN6Eca8jtPjgph7fhxainqB4APe9n5bbXqEXnR4SvD7lNfry6frr5ra429583ny8KywnTVmIrpbSVJpZymvSMsIkI1xYUeXzUpvOgDasFU1nLa9M1TY5aM0bWUJblWv0fum6j-HnDGlSo0sWhkF7CHNSVc0ol5xm8GIBbQwpRejUPrpRx0dFiTqKVjurjqLVUXTG3576zmaE9h98MpuBdydAJ6uHLmpvXfrLMSqYKPNYI75whzBMENOPYT5AVD3oYeoVycGrOv8uIZKIvCvypGUuK5cy8G2w0Xn4417twhx91vn_Vz8BsC2mzg</recordid><startdate>200905</startdate><enddate>200905</enddate><creator>Robker, Rebecca L.</creator><creator>Akison, Lisa K.</creator><creator>Bennett, Brenton D.</creator><creator>Thrupp, Penny N.</creator><creator>Chura, Lindsay R.</creator><creator>Russell, Darryl L.</creator><creator>Lane, Michelle</creator><creator>Norman, Robert J.</creator><general>Endocrine Society</general><general>Copyright by The Endocrine Society</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>200905</creationdate><title>Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared with Moderate-Weight Women</title><author>Robker, Rebecca L. ; Akison, Lisa K. ; Bennett, Brenton D. ; Thrupp, Penny N. ; Chura, Lindsay R. ; Russell, Darryl L. ; Lane, Michelle ; Norman, Robert J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4083-5f799b6a2c1470d20292045c56c403abfbeab2d58fcc46b6d8888174893ed63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Androgens - metabolism</topic><topic>Biological and medical sciences</topic><topic>Body Mass Index</topic><topic>Body Weight - genetics</topic><topic>Body Weight - physiology</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cumulus Cells - metabolism</topic><topic>Endocrinopathies</topic><topic>Feeding. 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Psychology</topic><topic>Gene Expression - physiology</topic><topic>Granulosa Cells - metabolism</topic><topic>Hormones - biosynthesis</topic><topic>Hormones - genetics</topic><topic>Hormones - metabolism</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Obesity - genetics</topic><topic>Obesity - metabolism</topic><topic>Oocytes - physiology</topic><topic>Ovary - metabolism</topic><topic>Reproduction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - biosynthesis</topic><topic>RNA - isolation &amp; purification</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Robker, Rebecca L.</creatorcontrib><creatorcontrib>Akison, Lisa K.</creatorcontrib><creatorcontrib>Bennett, Brenton D.</creatorcontrib><creatorcontrib>Thrupp, Penny N.</creatorcontrib><creatorcontrib>Chura, Lindsay R.</creatorcontrib><creatorcontrib>Russell, Darryl L.</creatorcontrib><creatorcontrib>Lane, Michelle</creatorcontrib><creatorcontrib>Norman, Robert J.</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>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Robker, Rebecca L.</au><au>Akison, Lisa K.</au><au>Bennett, Brenton D.</au><au>Thrupp, Penny N.</au><au>Chura, Lindsay R.</au><au>Russell, Darryl L.</au><au>Lane, Michelle</au><au>Norman, Robert J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared with Moderate-Weight Women</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2009-05</date><risdate>2009</risdate><volume>94</volume><issue>5</issue><spage>1533</spage><epage>1540</epage><pages>1533-1540</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context: Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period. Objective: This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence. Design, Setting, and Participants: Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33; BMI 20–24.9 kg/m2), overweight (n = 31; BMI 25–29.9 kg/m2), and obese (n =32; BMI ≥30 kg/m2). Intervention: For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes. Main Outcome Measures: Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance. Results: Increasing BMI was associated with increased follicular fluid insulin (P &lt; 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P &lt; 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women. Conclusions: Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients. Increasing body mass index is associated with alterations in the ovarian follicular environment.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>19223519</pmid><doi>10.1210/jc.2008-2648</doi><tpages>8</tpages></addata></record>
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subjects Adult
Androgens - metabolism
Biological and medical sciences
Body Mass Index
Body Weight - genetics
Body Weight - physiology
C-Reactive Protein - metabolism
Cumulus Cells - metabolism
Endocrinopathies
Feeding. Feeding behavior
Female
Follicular Fluid - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression - physiology
Granulosa Cells - metabolism
Hormones - biosynthesis
Hormones - genetics
Hormones - metabolism
Humans
Medical sciences
Obesity - genetics
Obesity - metabolism
Oocytes - physiology
Ovary - metabolism
Reproduction
Reverse Transcriptase Polymerase Chain Reaction
RNA - biosynthesis
RNA - isolation & purification
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
title Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared with Moderate-Weight Women
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