Estrogen Receptor α Is a Major Contributor to Estrogen-Mediated Fetal Testis Dysgenesis and Cryptorchidism
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| Název: | Estrogen Receptor α Is a Major Contributor to Estrogen-Mediated Fetal Testis Dysgenesis and Cryptorchidism |
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| Autoři: | Cederroth, Christopher, Schaad, Olivier, Descombes, Patrick, Chambon, Pierre, Vassalli, Jean-Dominique, Nef, Serge |
| Zdroj: | Endocrinology, Vol. 148, No 11 (2007) pp. 5507-19 |
| Informace o vydavateli: | The Endocrine Society, 2007. |
| Rok vydání: | 2007 |
| Témata: | 576.5, Male, 0301 basic medicine, Estrogens/toxicity, Mice, Transgenic, Cryptorchidism/chemically induced/embryology/genetics, Gonadal Dysgenesis/chemically induced/embryology/genetics, Gonadal Dysgenesis, Models, Biological, Mice, 03 medical and health sciences, Fetus, Estrogen Receptor alpha/genetics/physiology, Pregnancy, Cryptorchidism, Testis, Diethylstilbestrol/toxicity, Animals, ddc:576.5, Genetic Predisposition to Disease, Fetus/drug effects/metabolism, Diethylstilbestrol, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Gene Expression Regulation, Developmental/drug effects, Gene Expression Profiling, Estrogen Receptor alpha, Testis/drug effects/embryology/metabolism, Gene Expression Regulation, Developmental, Estrogens, Prenatal Exposure Delayed Effects/genetics, Mice, Inbred C57BL, Prenatal Exposure Delayed Effects, Female |
| Popis: | Failure of the testes to descend into the scrotum (cryptorchidism) is one of the most common birth defects in humans. In utero exposure to estrogens, such as 17beta-estradiol (E2) or the synthetic estrogen diethylstilbestrol (DES), down-regulates insulin-like 3 (Insl3) expression in embryonic Leydig cells, which in turn results in cryptorchidism in mice. To identify the molecular mechanism whereby xenoestrogens block Insl3 gene transcription, we performed a microarray analysis of wild-type or estrogen receptor (ER) alpha-mutant testes exposed in utero to pharmacological doses of E2 or DES. Six and 31 genes were respectively down-regulated and up-regulated by estrogen exposure (> or =4-fold). All six genes down-regulated by estrogen exposure, including Insl3 and the steroidogenic genes steroidogenic acute regulatory protein and cytochrome P450 17alpha-hydroxylase/17,20-lyase, were done so by an ERalpha-dependent mechanism. In contrast, up-regulation was mediated either by ERalpha for 12 genes or by an independent mechanism for the 19 remaining genes. Finally, we show that Insl3 gene expression and testicular descent were not affected by in utero exposure to E2 or DES in ERalpha mutant mice, whereas absence of ERbeta did not influence the effect of these estrogens. Collectively, these data demonstrate that xenoestrogens inhibit the endocrine functions of fetal Leydig cells through an ERalpha-dependent mechanism. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2007-0689 |
| Přístupová URL adresa: | https://academic.oup.com/endo/article-pdf/148/11/5507/10726509/endo5507.pdf https://pubmed.ncbi.nlm.nih.gov/17673513 https://www.ncbi.nlm.nih.gov/pubmed/17673513 http://press.endocrine.org/doi/abs/10.1210/en.2007-0689 https://archive-ouverte.unige.ch/unige:3910/ATTACHMENT02 https://academic.oup.com/endo/article/148/11/5507/2501600 https://hal.archives-ouvertes.fr/hal-00188842 https://europepmc.org/article/MED/17673513 https://archive-ouverte.unige.ch/unige:3910 https://archive-ouverte.unige.ch/unige:3910 https://doi.org/10.1210/en.2007-0689 |
| Přístupové číslo: | edsair.doi.dedup.....162864329efeac8e9095d1b2da8d65c9 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Failure of the testes to descend into the scrotum (cryptorchidism) is one of the most common birth defects in humans. In utero exposure to estrogens, such as 17beta-estradiol (E2) or the synthetic estrogen diethylstilbestrol (DES), down-regulates insulin-like 3 (Insl3) expression in embryonic Leydig cells, which in turn results in cryptorchidism in mice. To identify the molecular mechanism whereby xenoestrogens block Insl3 gene transcription, we performed a microarray analysis of wild-type or estrogen receptor (ER) alpha-mutant testes exposed in utero to pharmacological doses of E2 or DES. Six and 31 genes were respectively down-regulated and up-regulated by estrogen exposure (> or =4-fold). All six genes down-regulated by estrogen exposure, including Insl3 and the steroidogenic genes steroidogenic acute regulatory protein and cytochrome P450 17alpha-hydroxylase/17,20-lyase, were done so by an ERalpha-dependent mechanism. In contrast, up-regulation was mediated either by ERalpha for 12 genes or by an independent mechanism for the 19 remaining genes. Finally, we show that Insl3 gene expression and testicular descent were not affected by in utero exposure to E2 or DES in ERalpha mutant mice, whereas absence of ERbeta did not influence the effect of these estrogens. Collectively, these data demonstrate that xenoestrogens inhibit the endocrine functions of fetal Leydig cells through an ERalpha-dependent mechanism. |
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| ISSN: | 19457170 00137227 |
| DOI: | 10.1210/en.2007-0689 |