Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences
Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development an...
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| Veröffentlicht in: | Scientific reports 2016-01, Vol.6 (1), p.19789, Article 19789 |
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| creator | Dean, Afshan van den Driesche, Sander Wang, Yili McKinnell, Chris Macpherson, Sheila Eddie, Sharon L. Kinnell, Hazel Hurtado-Gonzalez, Pablo Chambers, Tom J. Stevenson, Kerrie Wolfinger, Elke Hrabalkova, Lenka Calarrao, Ana Bayne, Rosey AL Hagen, Casper P. Mitchell, Rod T. Anderson, Richard A. Sharpe, Richard M. |
| description | Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters. |
| doi_str_mv | 10.1038/srep19789 |
| format | Article |
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As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep19789</identifier><identifier>PMID: 26813099</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/136/2434/1706 ; 631/443/494/2732/1577 ; Acetaminophen ; Analgesics ; Analgesics - pharmacology ; Animals ; Cell Differentiation ; Female ; Females ; Fertility ; Fetus ; Fetuses ; Germ cells ; Germ Cells - cytology ; Germ Cells - drug effects ; Humanities and Social Sciences ; Indomethacin ; Male ; Males ; Maternal Exposure ; Meiosis ; multidisciplinary ; Offspring ; Oogonia ; Ovaries ; Phenotype ; Pregnancy ; Prenatal Exposure Delayed Effects ; Prostaglandins - metabolism ; Puberty ; Rats ; Reproduction - drug effects ; Rodents ; Science</subject><ispartof>Scientific reports, 2016-01, Vol.6 (1), p.19789, Article 19789</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Jan 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-f27568952879bdf149ee07b7eb86046552bee19731206c9fafdb33cdbcd213933</citedby><cites>FETCH-LOGICAL-c438t-f27568952879bdf149ee07b7eb86046552bee19731206c9fafdb33cdbcd213933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728385/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728385/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26813099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dean, Afshan</creatorcontrib><creatorcontrib>van den Driesche, Sander</creatorcontrib><creatorcontrib>Wang, Yili</creatorcontrib><creatorcontrib>McKinnell, Chris</creatorcontrib><creatorcontrib>Macpherson, Sheila</creatorcontrib><creatorcontrib>Eddie, Sharon L.</creatorcontrib><creatorcontrib>Kinnell, Hazel</creatorcontrib><creatorcontrib>Hurtado-Gonzalez, Pablo</creatorcontrib><creatorcontrib>Chambers, Tom J.</creatorcontrib><creatorcontrib>Stevenson, Kerrie</creatorcontrib><creatorcontrib>Wolfinger, Elke</creatorcontrib><creatorcontrib>Hrabalkova, Lenka</creatorcontrib><creatorcontrib>Calarrao, Ana</creatorcontrib><creatorcontrib>Bayne, Rosey AL</creatorcontrib><creatorcontrib>Hagen, Casper P.</creatorcontrib><creatorcontrib>Mitchell, Rod T.</creatorcontrib><creatorcontrib>Anderson, Richard A.</creatorcontrib><creatorcontrib>Sharpe, Richard M.</creatorcontrib><title>Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters.</description><subject>631/136/2434/1706</subject><subject>631/443/494/2732/1577</subject><subject>Acetaminophen</subject><subject>Analgesics</subject><subject>Analgesics - pharmacology</subject><subject>Animals</subject><subject>Cell Differentiation</subject><subject>Female</subject><subject>Females</subject><subject>Fertility</subject><subject>Fetus</subject><subject>Fetuses</subject><subject>Germ cells</subject><subject>Germ Cells - cytology</subject><subject>Germ Cells - drug effects</subject><subject>Humanities and Social Sciences</subject><subject>Indomethacin</subject><subject>Male</subject><subject>Males</subject><subject>Maternal Exposure</subject><subject>Meiosis</subject><subject>multidisciplinary</subject><subject>Offspring</subject><subject>Oogonia</subject><subject>Ovaries</subject><subject>Phenotype</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Prostaglandins - metabolism</subject><subject>Puberty</subject><subject>Rats</subject><subject>Reproduction - drug 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with inter-generational reproductive consequences</title><author>Dean, Afshan ; van den Driesche, Sander ; Wang, Yili ; McKinnell, Chris ; Macpherson, Sheila ; Eddie, Sharon L. ; Kinnell, Hazel ; Hurtado-Gonzalez, Pablo ; Chambers, Tom J. ; Stevenson, Kerrie ; Wolfinger, Elke ; Hrabalkova, Lenka ; Calarrao, Ana ; Bayne, Rosey AL ; Hagen, Casper P. ; Mitchell, Rod T. ; Anderson, Richard A. ; Sharpe, Richard M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-f27568952879bdf149ee07b7eb86046552bee19731206c9fafdb33cdbcd213933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>631/136/2434/1706</topic><topic>631/443/494/2732/1577</topic><topic>Acetaminophen</topic><topic>Analgesics</topic><topic>Analgesics - pharmacology</topic><topic>Animals</topic><topic>Cell 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Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dean, Afshan</au><au>van den Driesche, Sander</au><au>Wang, Yili</au><au>McKinnell, Chris</au><au>Macpherson, Sheila</au><au>Eddie, Sharon L.</au><au>Kinnell, Hazel</au><au>Hurtado-Gonzalez, Pablo</au><au>Chambers, Tom J.</au><au>Stevenson, Kerrie</au><au>Wolfinger, Elke</au><au>Hrabalkova, Lenka</au><au>Calarrao, Ana</au><au>Bayne, Rosey AL</au><au>Hagen, Casper P.</au><au>Mitchell, Rod T.</au><au>Anderson, Richard A.</au><au>Sharpe, Richard M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-01-27</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>19789</spage><pages>19789-</pages><artnum>19789</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26813099</pmid><doi>10.1038/srep19789</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/136/2434/1706 631/443/494/2732/1577 Acetaminophen Analgesics Analgesics - pharmacology Animals Cell Differentiation Female Females Fertility Fetus Fetuses Germ cells Germ Cells - cytology Germ Cells - drug effects Humanities and Social Sciences Indomethacin Male Males Maternal Exposure Meiosis multidisciplinary Offspring Oogonia Ovaries Phenotype Pregnancy Prenatal Exposure Delayed Effects Prostaglandins - metabolism Puberty Rats Reproduction - drug effects Rodents Science |
| title | Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences |
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