Prostaglandins, masculinization and its disorders: effects of fetal exposure of the rat to the cyclooxygenase inhibitor- indomethacin
Recent studies have established that masculinization of the male reproductive tract is programmed by androgens in a critical fetal 'masculinization programming window' (MPW). What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice impl...
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| description | Recent studies have established that masculinization of the male reproductive tract is programmed by androgens in a critical fetal 'masculinization programming window' (MPW). What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice implicated prostaglandin (PG)-mediation of androgen-induced masculinization, but this has never been followed up. We therefore investigated if PGs might mediate androgen effects in the MPW by exposing pregnant rats to indomethacin (which blocks PG production by inhibiting cyclooxygenase activity) during this period and then examining if androgen production or action (masculinization) was affected. Pregnant rats were treated with indomethacin (0.8 mg/kg/day; e15.5-e18.5) to encompass the MPW. Indomethacin exposure decreased fetal bodyweight (e21.5), testis weight (e21.5) and testicular PGE2 (e17.5, e21.5), but had no effect on intratesticular testosterone (ITT; e17.5) or anogenital index (AGI; e21.5). Postnatally, AGI, testis weight and blood testosterone were unaffected by indomethacin exposure and no cryptorchidism or hypospadias occurred. Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% (p |
| doi_str_mv | 10.1371/journal.pone.0062556 |
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What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice implicated prostaglandin (PG)-mediation of androgen-induced masculinization, but this has never been followed up. We therefore investigated if PGs might mediate androgen effects in the MPW by exposing pregnant rats to indomethacin (which blocks PG production by inhibiting cyclooxygenase activity) during this period and then examining if androgen production or action (masculinization) was affected. Pregnant rats were treated with indomethacin (0.8 mg/kg/day; e15.5-e18.5) to encompass the MPW. Indomethacin exposure decreased fetal bodyweight (e21.5), testis weight (e21.5) and testicular PGE2 (e17.5, e21.5), but had no effect on intratesticular testosterone (ITT; e17.5) or anogenital index (AGI; e21.5). Postnatally, AGI, testis weight and blood testosterone were unaffected by indomethacin exposure and no cryptorchidism or hypospadias occurred. Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% (p<0.001) in adulthood, an effect that is unexplained. Our results demonstrate that indomethacin can effectively decrease intra-testicular PGE2 level. However, the resulting male phenotype does not support a role for PGs in mediating androgen-induced masculinization during the MPW in rats. The contrast with previous mouse studies is unexplained but may reflect a species difference.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0062556</identifier><identifier>PMID: 23671609</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Analgesics ; Androgens ; Animals ; Anogenital ; Aspirin ; Biology ; COX-2 inhibitors ; Cryptorchidism ; Cryptorchidism - chemically induced ; Cryptorchidism - metabolism ; Cyclooxygenase Inhibitors - toxicity ; Dinoprostone - metabolism ; Epidemiology ; Exposure ; Female ; Fetal Development - drug effects ; Fetuses ; Humans ; Hypospadias - chemically induced ; Hypospadias - metabolism ; Indomethacin ; Indomethacin - toxicity ; Induced labor ; Male ; Mediation ; Medical research ; Medicine ; Mice ; Organ Size - drug effects ; Penis ; Pregnancy ; Prenatal exposure ; Prenatal Exposure Delayed Effects - chemically induced ; Prenatal Exposure Delayed Effects - metabolism ; Prostaglandin E2 ; Prostaglandin endoperoxide synthase ; Prostaglandins ; Puberty ; Rats ; Rats, Wistar ; Reproductive health ; Reproductive system ; Rodents ; Studies ; Testes ; Testis - drug effects ; Testis - metabolism ; Testis - pathology ; Testosterone ; Testosterone - metabolism</subject><ispartof>PloS one, 2013-05, Vol.8 (5), p.e62556</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Dean et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Dean et al 2013 Dean et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-877e913738a0772cac3ee6ffa62f2a97fba81cddd80e53cbbf5a7d812cf3128b3</citedby><cites>FETCH-LOGICAL-c692t-877e913738a0772cac3ee6ffa62f2a97fba81cddd80e53cbbf5a7d812cf3128b3</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/PMC3643956/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643956/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23671609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lobaccaro, Jean-Marc A.</contributor><creatorcontrib>Dean, Afshan</creatorcontrib><creatorcontrib>Mungall, William</creatorcontrib><creatorcontrib>McKinnell, Chris</creatorcontrib><creatorcontrib>Sharpe, Richard M</creatorcontrib><title>Prostaglandins, masculinization and its disorders: effects of fetal exposure of the rat to the cyclooxygenase inhibitor- indomethacin</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Recent studies have established that masculinization of the male reproductive tract is programmed by androgens in a critical fetal 'masculinization programming window' (MPW). 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Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% (p<0.001) in adulthood, an effect that is unexplained. Our results demonstrate that indomethacin can effectively decrease intra-testicular PGE2 level. However, the resulting male phenotype does not support a role for PGs in mediating androgen-induced masculinization during the MPW in rats. 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What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice implicated prostaglandin (PG)-mediation of androgen-induced masculinization, but this has never been followed up. We therefore investigated if PGs might mediate androgen effects in the MPW by exposing pregnant rats to indomethacin (which blocks PG production by inhibiting cyclooxygenase activity) during this period and then examining if androgen production or action (masculinization) was affected. Pregnant rats were treated with indomethacin (0.8 mg/kg/day; e15.5-e18.5) to encompass the MPW. Indomethacin exposure decreased fetal bodyweight (e21.5), testis weight (e21.5) and testicular PGE2 (e17.5, e21.5), but had no effect on intratesticular testosterone (ITT; e17.5) or anogenital index (AGI; e21.5). Postnatally, AGI, testis weight and blood testosterone were unaffected by indomethacin exposure and no cryptorchidism or hypospadias occurred. Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% (p<0.001) in adulthood, an effect that is unexplained. Our results demonstrate that indomethacin can effectively decrease intra-testicular PGE2 level. However, the resulting male phenotype does not support a role for PGs in mediating androgen-induced masculinization during the MPW in rats. The contrast with previous mouse studies is unexplained but may reflect a species difference.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23671609</pmid><doi>10.1371/journal.pone.0062556</doi><tpages>e62556</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Analgesics Androgens Animals Anogenital Aspirin Biology COX-2 inhibitors Cryptorchidism Cryptorchidism - chemically induced Cryptorchidism - metabolism Cyclooxygenase Inhibitors - toxicity Dinoprostone - metabolism Epidemiology Exposure Female Fetal Development - drug effects Fetuses Humans Hypospadias - chemically induced Hypospadias - metabolism Indomethacin Indomethacin - toxicity Induced labor Male Mediation Medical research Medicine Mice Organ Size - drug effects Penis Pregnancy Prenatal exposure Prenatal Exposure Delayed Effects - chemically induced Prenatal Exposure Delayed Effects - metabolism Prostaglandin E2 Prostaglandin endoperoxide synthase Prostaglandins Puberty Rats Rats, Wistar Reproductive health Reproductive system Rodents Studies Testes Testis - drug effects Testis - metabolism Testis - pathology Testosterone Testosterone - metabolism |
| title | Prostaglandins, masculinization and its disorders: effects of fetal exposure of the rat to the cyclooxygenase inhibitor- indomethacin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T18%3A45%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prostaglandins,%20masculinization%20and%20its%20disorders:%20effects%20of%20fetal%20exposure%20of%20the%20rat%20to%20the%20cyclooxygenase%20inhibitor-%20indomethacin&rft.jtitle=PloS%20one&rft.au=Dean,%20Afshan&rft.date=2013-05-03&rft.volume=8&rft.issue=5&rft.spage=e62556&rft.pages=e62556-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0062556&rft_dat=%3Cgale_plos_%3EA478436179%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1350377092&rft_id=info:pmid/23671609&rft_galeid=A478436179&rft_doaj_id=oai_doaj_org_article_7a1536a9e0a04528b96c1e0db0725a55&rfr_iscdi=true |