Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels

Objective To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biol...

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Veröffentlicht in:Fertility and sterility 2015-11, Vol.104 (5), p.1294-1301.e1
Hauptverfasser: Bøtkjær, Jane Alrø, M.Sc, Jeppesen, Janni Vikkelsø, Ph.D, Wissing, Marie Louise, Ph.D, Kløverpris, Søren, Ph.D, Oxvig, Claus, D.M.Sc, Mason, J. Ian, Ph.D, Borgbo, Tanni, Ph.D, Andersen, Claus Yding, D.M.Sc
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container_end_page 1301.e1
container_issue 5
container_start_page 1294
container_title Fertility and sterility
container_volume 104
creator Bøtkjær, Jane Alrø, M.Sc
Jeppesen, Janni Vikkelsø, Ph.D
Wissing, Marie Louise, Ph.D
Kløverpris, Søren, Ph.D
Oxvig, Claus, D.M.Sc
Mason, J. Ian, Ph.D
Borgbo, Tanni, Ph.D
Andersen, Claus Yding, D.M.Sc
description Objective To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological activity of PAPP-A in FF was evaluated. Design Laboratory investigation. Setting University hospital. Patient(s) A total of 43 women with a total of 80 samples were obtained from three different size-groups of antral follicles collected before and after the LH surge. Intervention(s) ELISA measurement of steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on follicles of different diameter, and proteolytic activity of PAPP-A toward insulin-like growth factor (IGF)–binding protein 4 (IGFBP-4). Main Outcome Measure(s) Association between FF levels of PAPP-A and measured ovarian hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in antral follicles. Result(s) A highly significant association between FF levels of PAPP-A and all measured hormones were obtained with positive associations toward E2 and P, whereas AMH, T, and A showed strong negative associations. PAPP-A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A immunostaining shifted from being primarily present in theca cells of small antral follicles to being expressed in granulosa cells (GCs) of preovulatory follicles. In contrast, AMH expression became reduced with increasing follicular diameter. Aromatase expression was highly specifically localized to GCs of preovulatory follicles. Conclusion(s) The results suggest that PAPP-A is specifically involved in the regulation of steroidogenesis in human antral follicles. Local regulation of IGF-II activity may represent a mechanism by which PAPP-A exerts this function and highlights the importance of IGF signaling during follicular development.
doi_str_mv 10.1016/j.fertnstert.2015.07.1152
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Ian, Ph.D ; Borgbo, Tanni, Ph.D ; Andersen, Claus Yding, D.M.Sc</creator><creatorcontrib>Bøtkjær, Jane Alrø, M.Sc ; Jeppesen, Janni Vikkelsø, Ph.D ; Wissing, Marie Louise, Ph.D ; Kløverpris, Søren, Ph.D ; Oxvig, Claus, D.M.Sc ; Mason, J. Ian, Ph.D ; Borgbo, Tanni, Ph.D ; Andersen, Claus Yding, D.M.Sc</creatorcontrib><description>Objective To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological activity of PAPP-A in FF was evaluated. Design Laboratory investigation. Setting University hospital. Patient(s) A total of 43 women with a total of 80 samples were obtained from three different size-groups of antral follicles collected before and after the LH surge. Intervention(s) ELISA measurement of steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on follicles of different diameter, and proteolytic activity of PAPP-A toward insulin-like growth factor (IGF)–binding protein 4 (IGFBP-4). Main Outcome Measure(s) Association between FF levels of PAPP-A and measured ovarian hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in antral follicles. Result(s) A highly significant association between FF levels of PAPP-A and all measured hormones were obtained with positive associations toward E2 and P, whereas AMH, T, and A showed strong negative associations. PAPP-A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A immunostaining shifted from being primarily present in theca cells of small antral follicles to being expressed in granulosa cells (GCs) of preovulatory follicles. In contrast, AMH expression became reduced with increasing follicular diameter. Aromatase expression was highly specifically localized to GCs of preovulatory follicles. Conclusion(s) The results suggest that PAPP-A is specifically involved in the regulation of steroidogenesis in human antral follicles. Local regulation of IGF-II activity may represent a mechanism by which PAPP-A exerts this function and highlights the importance of IGF signaling during follicular development.</description><identifier>ISSN: 0015-0282</identifier><identifier>EISSN: 1556-5653</identifier><identifier>DOI: 10.1016/j.fertnstert.2015.07.1152</identifier><identifier>PMID: 26297643</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>AMH ; Androstenedione - metabolism ; Anti-Mullerian Hormone - metabolism ; aromatase ; Aromatase - metabolism ; Enzyme-Linked Immunosorbent Assay ; Estradiol - metabolism ; Female ; Follicular Fluid - enzymology ; Hospitals, University ; human follicles ; human ovarian steroidogenesis ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor Binding Protein 4 - metabolism ; Internal Medicine ; Menstrual Cycle - metabolism ; Obstetrics and Gynecology ; Ovarian Follicle - enzymology ; PAPP-A ; Pregnancy-Associated Plasma Protein-A - metabolism ; Proteolysis ; Signal Transduction ; Testosterone - metabolism</subject><ispartof>Fertility and sterility, 2015-11, Vol.104 (5), p.1294-1301.e1</ispartof><rights>American Society for Reproductive Medicine</rights><rights>2015 American Society for Reproductive Medicine</rights><rights>Copyright © 2015 American Society for Reproductive Medicine. 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All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-a1e8d9870bb09ca54e3c41f5ff1462b99605c201fee3f5c640bfcc09615965f33</citedby><cites>FETCH-LOGICAL-c553t-a1e8d9870bb09ca54e3c41f5ff1462b99605c201fee3f5c640bfcc09615965f33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0015028215016647$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26297643$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bøtkjær, Jane Alrø, M.Sc</creatorcontrib><creatorcontrib>Jeppesen, Janni Vikkelsø, Ph.D</creatorcontrib><creatorcontrib>Wissing, Marie Louise, Ph.D</creatorcontrib><creatorcontrib>Kløverpris, Søren, Ph.D</creatorcontrib><creatorcontrib>Oxvig, Claus, D.M.Sc</creatorcontrib><creatorcontrib>Mason, J. Ian, Ph.D</creatorcontrib><creatorcontrib>Borgbo, Tanni, Ph.D</creatorcontrib><creatorcontrib>Andersen, Claus Yding, D.M.Sc</creatorcontrib><title>Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels</title><title>Fertility and sterility</title><addtitle>Fertil Steril</addtitle><description>Objective To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological activity of PAPP-A in FF was evaluated. Design Laboratory investigation. Setting University hospital. Patient(s) A total of 43 women with a total of 80 samples were obtained from three different size-groups of antral follicles collected before and after the LH surge. Intervention(s) ELISA measurement of steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on follicles of different diameter, and proteolytic activity of PAPP-A toward insulin-like growth factor (IGF)–binding protein 4 (IGFBP-4). Main Outcome Measure(s) Association between FF levels of PAPP-A and measured ovarian hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in antral follicles. Result(s) A highly significant association between FF levels of PAPP-A and all measured hormones were obtained with positive associations toward E2 and P, whereas AMH, T, and A showed strong negative associations. PAPP-A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A immunostaining shifted from being primarily present in theca cells of small antral follicles to being expressed in granulosa cells (GCs) of preovulatory follicles. In contrast, AMH expression became reduced with increasing follicular diameter. Aromatase expression was highly specifically localized to GCs of preovulatory follicles. Conclusion(s) The results suggest that PAPP-A is specifically involved in the regulation of steroidogenesis in human antral follicles. Local regulation of IGF-II activity may represent a mechanism by which PAPP-A exerts this function and highlights the importance of IGF signaling during follicular development.</description><subject>AMH</subject><subject>Androstenedione - metabolism</subject><subject>Anti-Mullerian Hormone - metabolism</subject><subject>aromatase</subject><subject>Aromatase - metabolism</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Estradiol - metabolism</subject><subject>Female</subject><subject>Follicular Fluid - enzymology</subject><subject>Hospitals, University</subject><subject>human follicles</subject><subject>human ovarian steroidogenesis</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Insulin-Like Growth Factor Binding Protein 4 - metabolism</subject><subject>Internal Medicine</subject><subject>Menstrual Cycle - metabolism</subject><subject>Obstetrics and Gynecology</subject><subject>Ovarian Follicle - enzymology</subject><subject>PAPP-A</subject><subject>Pregnancy-Associated Plasma Protein-A - metabolism</subject><subject>Proteolysis</subject><subject>Signal Transduction</subject><subject>Testosterone - metabolism</subject><issn>0015-0282</issn><issn>1556-5653</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkkFv1DAQhS1ERbeFv4DMjUuC7cTO5oJUrUpbqRJIwNlynDHrxbEX21nYf19Hu4DEicu8w7w3o_k0CL2hpKaEine72kDMPuVSa0Yor0lXU8rZM7SinIuKC948RytSWhVha3aJrlLaEUIE7dgLdMkE6zvRNiv061OEb155faxUSkFblWHEe6fSpPA-hgzW4xtcynaelMfhoKItaoJzVjtIWPkR21z0HLfB4582b0smR3XyzU5FvA1xCh6wgwO49BJdGOUSvDrrNfr64fbL5r56_Hj3sLl5rDTnTa4UhfXYrzsyDKTXirfQ6JYabgxtBRv6XhCuCwID0BiuRUsGozXpBeW94KZprtHb09xyzI8ZUpaTTRqcUx7CnGQB0jecUbFY-5NVx5BSBCP30U4qHiUlcgEvd_IveLmAl6STC_iSfX1eMw8TjH-Sv0kXw-ZkKLfDwUKUSVvwGkYbQWc5Bvtfa97_M0U7661W7jscIe3CHH2hKalMTBL5efmA5QFKpUK0XfMEc_6x4g</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>Bøtkjær, Jane Alrø, M.Sc</creator><creator>Jeppesen, Janni Vikkelsø, Ph.D</creator><creator>Wissing, Marie Louise, Ph.D</creator><creator>Kløverpris, Søren, Ph.D</creator><creator>Oxvig, Claus, D.M.Sc</creator><creator>Mason, J. Ian, Ph.D</creator><creator>Borgbo, Tanni, Ph.D</creator><creator>Andersen, Claus Yding, D.M.Sc</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20151101</creationdate><title>Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels</title><author>Bøtkjær, Jane Alrø, M.Sc ; Jeppesen, Janni Vikkelsø, Ph.D ; Wissing, Marie Louise, Ph.D ; Kløverpris, Søren, Ph.D ; Oxvig, Claus, D.M.Sc ; Mason, J. 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Ian, Ph.D</creatorcontrib><creatorcontrib>Borgbo, Tanni, Ph.D</creatorcontrib><creatorcontrib>Andersen, Claus Yding, D.M.Sc</creatorcontrib><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>Bøtkjær, Jane Alrø, M.Sc</au><au>Jeppesen, Janni Vikkelsø, Ph.D</au><au>Wissing, Marie Louise, Ph.D</au><au>Kløverpris, Søren, Ph.D</au><au>Oxvig, Claus, D.M.Sc</au><au>Mason, J. Ian, Ph.D</au><au>Borgbo, Tanni, Ph.D</au><au>Andersen, Claus Yding, D.M.Sc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels</atitle><jtitle>Fertility and sterility</jtitle><addtitle>Fertil Steril</addtitle><date>2015-11-01</date><risdate>2015</risdate><volume>104</volume><issue>5</issue><spage>1294</spage><epage>1301.e1</epage><pages>1294-1301.e1</pages><issn>0015-0282</issn><eissn>1556-5653</eissn><abstract>Objective To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological activity of PAPP-A in FF was evaluated. Design Laboratory investigation. Setting University hospital. Patient(s) A total of 43 women with a total of 80 samples were obtained from three different size-groups of antral follicles collected before and after the LH surge. Intervention(s) ELISA measurement of steroids, PAPP-A, and AMH, immunohistochemistry of PAPP-A, AMH, and aromatase on follicles of different diameter, and proteolytic activity of PAPP-A toward insulin-like growth factor (IGF)–binding protein 4 (IGFBP-4). Main Outcome Measure(s) Association between FF levels of PAPP-A and measured ovarian hormones, PAPP-A activity in FF, localization of PAPP-A, AMH, and aromatase in antral follicles. Result(s) A highly significant association between FF levels of PAPP-A and all measured hormones were obtained with positive associations toward E2 and P, whereas AMH, T, and A showed strong negative associations. PAPP-A proteolytic activity toward IGFBP-4 was detected in human FF. PAPP-A immunostaining shifted from being primarily present in theca cells of small antral follicles to being expressed in granulosa cells (GCs) of preovulatory follicles. In contrast, AMH expression became reduced with increasing follicular diameter. Aromatase expression was highly specifically localized to GCs of preovulatory follicles. Conclusion(s) The results suggest that PAPP-A is specifically involved in the regulation of steroidogenesis in human antral follicles. Local regulation of IGF-II activity may represent a mechanism by which PAPP-A exerts this function and highlights the importance of IGF signaling during follicular development.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26297643</pmid><doi>10.1016/j.fertnstert.2015.07.1152</doi><oa>free_for_read</oa></addata></record>
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ispartof Fertility and sterility, 2015-11, Vol.104 (5), p.1294-1301.e1
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source MEDLINE; Elsevier ScienceDirect Journals; Alma/SFX Local Collection; EZB Electronic Journals Library
subjects AMH
Androstenedione - metabolism
Anti-Mullerian Hormone - metabolism
aromatase
Aromatase - metabolism
Enzyme-Linked Immunosorbent Assay
Estradiol - metabolism
Female
Follicular Fluid - enzymology
Hospitals, University
human follicles
human ovarian steroidogenesis
Humans
Immunohistochemistry
Insulin-Like Growth Factor Binding Protein 4 - metabolism
Internal Medicine
Menstrual Cycle - metabolism
Obstetrics and Gynecology
Ovarian Follicle - enzymology
PAPP-A
Pregnancy-Associated Plasma Protein-A - metabolism
Proteolysis
Signal Transduction
Testosterone - metabolism
title Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels
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