{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:44:06Z","timestamp":1787013846540,"version":"build-2736575974"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,3,23]],"date-time":"2017-03-23T00:00:00Z","timestamp":1490227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["11110457"],"award-info":[{"award-number":["11110457"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["1120176"],"award-info":[{"award-number":["1120176"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Estradiol (E\n                    <jats:sub>2<\/jats:sub>\n                    ) is normally metabolized to hydroxyestradiols and methoxyestradiols by\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    1A1,\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    1B1 and\n                    <jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>\n                    . However, an altered production of these metabolites by a disturbed expression of these enzymes is associated with reproductive and non\u2010reproductive pathologies. In vitro studies suggest that increased hydroxyestradiols and methoxyestradiols intratesticular generation is related to male infertility, but no studies have explored whether infertile men have a disturbed testicular expression of the enzymes that generate these E\n                    <jats:sub>2<\/jats:sub>\n                    metabolites. The aim of this study was to assess\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    1A1,\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    1B1 and\n                    <jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>\n                    testicular expression at m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    and protein level in men with spermatogenic impairment. Seventeen men with primary spermatogenic failure (13 with Sertoli cell\u2010only syndrome and four with maturation arrest) and nine controls with normal spermatogenesis were subjected to testicular biopsy. m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    was quantified using real\u2010time\n                    <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n                    and protein expression was evaluated using western blot and immunohistochemistry followed by integrated optic density analysis. Besides, the effects of hydroxyestradiols and methoxyestradiols on testosterone\u2010induced transcriptional activity were evaluated in\n                    <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content>\n                    4 cells using a luciferase reporter assay system. Our results show that patients with Sertoli cell\u2010only syndrome had significantly elevated\n                    <jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>\n                    expression at the m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    level, higher\n                    <jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>\n                    immunoreactivity in their seminiferous tubules and increased protein expression of the soluble\n                    <jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>\n                    isoform (S\u2010\n                    <jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>\n                    ), whereas patients with maturation arrest had significantly elevated\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    1A1 m\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    levels and higher\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    1A1 immunoreactivity in interstitial space. Finally, 2\u2010hydroxyestradiol decreased testosterone\u2010induced transcriptional activity in Sertoli cells in\u00a0vitro. In conclusion, male infertility is related to disturbed testicular expression of the enzymes responsible for producing hydroxyestradiols and\/or methoxyestradiols. If these changes are related with increased intratesticular hydroxyestradiols and methoxyestradiols concentrations, they could elicit an impaired Sertoli cell function. Our results suggest\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    1A1 and\n                    <jats:styled-content style=\"fixed-case\">COMT<\/jats:styled-content>\n                    as new potential targets in treating male infertility.\n                  <\/jats:p>","DOI":"10.1111\/andr.12346","type":"journal-article","created":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T07:09:17Z","timestamp":1490339357000},"page":"486-494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Disturbed testicular expression of the estrogen\u2010metabolizing enzymes\n                    <scp>CYP<\/scp>\n                    1A1 and\n                    <scp>COMT<\/scp>\n                    in infertile men with primary spermatogenic failure: possible negative implications on Sertoli cells"],"prefix":"10.1111","volume":"5","author":[{"given":"A.","family":"Parada\u2010Bustamante","sequence":"first","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Molina","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Valencia","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Fl\u00f3rez","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Lardone","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Argando\u00f1a","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Piottante","sequence":"additional","affiliation":[{"name":"Pathology Department Cl\u00ednica Las Condes Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ebensperguer","sequence":"additional","affiliation":[{"name":"Urology Department San Borja\u2010Arriar\u00e1n Clinical Hospital Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. A.","family":"Orihuela","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Immunology University of Santiago and CEDENNA Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Castro","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047-2927.2012.00056.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(96)00085-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-70-6-943"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx700174w"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2008.02.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/boc.201500094"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32810f2e58"},{"key":"e_1_2_7_9_1","first-page":"4352","article-title":"Gene expression in colorectal cancer","volume":"62","author":"Birkenkamp\u2010Demtroder K","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.2.329"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/425589"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.04.009"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2014.25"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-11-0060"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx0498657"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308114100"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-032154"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2014.11.003"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-006-9308-7"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920021610151210164501"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.09.011"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2011.10.058"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.5.1230"},{"key":"e_1_2_7_24_1","first-page":"2","article-title":"Testicular biopsy score count\u2013a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males","volume":"1","author":"Johnsen SG","year":"1970","journal-title":"Hormones"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047-2927.2014.00240.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.07.1524"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gam057"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2009.01002.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12289"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-246991"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.2174\/18715206113139990144"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev003"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2605.2002.00376.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086649"},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0031-6997(24)01423-6","article-title":"Catechol\u2010O\u2010methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors","volume":"51","author":"Mannisto PT","year":"1999","journal-title":"Pharmacol Rev"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405970200"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.2144\/000112100"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.05.002"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209319200"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)66540-8"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.5.2057"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000369662"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.02.012"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.09.030"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-014-0360-7"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12576"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092425"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2006.03.008"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7262.2008.00333.x"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2013.07.005"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb1978.10.302"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2007.07.003"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000106900.66354.30"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2011.94"},{"key":"e_1_2_7_56_1","first-page":"158","article-title":"Endogenous estrogen metabolites as biomarkers for endometrial cancer via a novel method of liquid chromatography\u2010mass spectrometry with hollow fiber liquid\u2010phase microextraction","volume":"47","author":"Zhao H","year":"2015","journal-title":"Horm Metab Res"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/19.1.1"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12346","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T13:00:35Z","timestamp":1750165235000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.12346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,23]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1111\/andr.12346"],"URL":"https:\/\/doi.org\/10.1111\/andr.12346","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,23]]},"assertion":[{"value":"2016-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}