{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:47:27Z","timestamp":1791298047375,"version":"4.1.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p>\n                    <jats:italic>In utero<\/jats:italic>\n                    exposure to exogenous anti-androgenic compounds induces a wide range of abnormalities of the reproductive system, including hypospermatogenesis, cryptorchidism and hypospadias. By using rats exposed\n                    <jats:italic>in utero<\/jats:italic>\n                    to the anti-androgenic compound flutamide (0.4, 2 or 10 mg\/kg per day), it has been shown that hypospermatogenesis in adult testes could be related to (i) a long-term apoptosis in germ cells but not in somatic Leydig and Sertoli cells as evidenced by the TUNEL approach and (ii) alterations in the mRNA and protein expression of pro- (Bax, Bak, Bid) and anti-apoptotic (Bcl-2, Bcl-w) members of the Bcl-2 family. Indeed, the number of apoptotic germ cells increased with the dose of flutamide administered and the apoptotic germ cells were mainly detected at androgen-dependent stages VII\u2013VIII. Moreover, for the Bcl-2-related proteins that were expressed mainly in the germ cells, a decrease in the levels of anti-apoptotic peptides Bcl-w (60%,\n                    <jats:italic>P<\/jats:italic>\n                    =0.003) and Bcl-2 (90%,\n                    <jats:italic>P<\/jats:italic>\n                    =0.0001) was observed at 2 mg\/kg per day flutamide and an increase in levels of the pro-apoptotic Bax (2.3-fold,\n                    <jats:italic>P<\/jats:italic>\n                    =0.0004) was detected at 10 mg\/kg per day. In contrast, the levels of pro-apoptotic peptide Bak that was mainly expressed in somatic cells decreased (70%,\n                    <jats:italic>P<\/jats:italic>\n                    =0.0008) at 10 mg\/kg per day. Such alterations in Bcl-2-related peptides occurred mainly at the protein level except for Bcl-2 (72%,\n                    <jats:italic>P<\/jats:italic>\n                    =0.0001) and Bak (43%,\n                    <jats:italic>P<\/jats:italic>\n                    =00002) transcripts. Together, these results showed that the apoptosis observed in adult germ cells from rats exposed\n                    <jats:italic>in utero<\/jats:italic>\n                    to flutamide may result from a long-term alteration in the balance between pro- and anti-apoptotic Bcl-2-related molecules in favour of pro-apoptotic proteins. These data further supported the concept of an androgen-dependent fetal programming that is in relation with an alteration of the expression of Bcl-2-related genes\/proteins promoting apoptosis in testicular germ cells of adult rats with fetal androgen disruption.\n                  <\/jats:p>","DOI":"10.1677\/joe.1.05771","type":"journal-article","created":{"date-parts":[[2004,12,2]],"date-time":"2004-12-02T18:42:13Z","timestamp":1102012933000},"page":"79-90","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":38,"title":["The mitochondrial-dependent pathway is chronically affected in testicular germ cell death in adult rats exposed in utero to anti-androgens"],"prefix":"10.1530","volume":"183","author":[{"given":"A","family":"Bozec","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Chuzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Chater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Paulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Bars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Benahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Mauduit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/183\/1\/1830079.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/183\/1\/1830079.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:28Z","timestamp":1784555728000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/183\/1\/79-90\/20792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1677\/joe.1.05771","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10]]}}}