Differential Effects of Bisphenol A and Diethylstilbestrol on Human, Rat and Mouse Fetal Leydig Cell Function
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{"title"=>"Differential Effects of Bisphenol A and Diethylstilbestrol on Human, Rat and Mouse Fetal Leydig Cell Function", "type"=>"journal", "authors"=>[{"first_name"=>"Thierry", "last_name"=>"N'Tumba-Byn", "scopus_author_id"=>"55383786800"}, {"first_name"=>"Delphine", "last_name"=>"Moison", "scopus_author_id"=>"6506351451"}, {"first_name"=>"Marlène", "last_name"=>"Lacroix", "scopus_author_id"=>"36114515800"}, {"first_name"=>"Charlotte", "last_name"=>"Lecureuil", "scopus_author_id"=>"6508345610"}, {"first_name"=>"Laëtitia", "last_name"=>"Lesage", "scopus_author_id"=>"55532139000"}, {"first_name"=>"Sophie M.", "last_name"=>"Prud'homme", "scopus_author_id"=>"54938881100"}, {"first_name"=>"Stéphanie", "last_name"=>"Pozzi-Gaudin", "scopus_author_id"=>"55532643200"}, {"first_name"=>"René", "last_name"=>"Frydman", "scopus_author_id"=>"7201860833"}, {"first_name"=>"Alexandra", "last_name"=>"Benachi", "scopus_author_id"=>"56262899200"}, {"first_name"=>"Gabriel", "last_name"=>"Livera", "scopus_author_id"=>"6603272688"}, {"first_name"=>"Virginie", "last_name"=>"Rouiller-Fabre", "scopus_author_id"=>"6602422855"}, {"first_name"=>"René", "last_name"=>"Habert", "scopus_author_id"=>"7003894209"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84871274369", "doi"=>"10.1371/journal.pone.0051579", "pui"=>"366298658", "pmid"=>"23284716", "scopus"=>"2-s2.0-84871274369", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"a7be3aee-943b-3c15-bbc1-399f481331ae", "abstract"=>"Endocrine disruptors (ED) have been incriminated in the current increase of male reproductive alterations. Bisphenol A (BPA) is a widely used weak estrogenic environmental ED and it is debated whether BPA concentrations within the average internal exposure are toxic. In the present study we investigated the effects of 10(-12) to 10(-5) M BPA concentrations on fetal Leydig cell function, as fetal life is a critical period of sensitivity to ED effects on male reproductive function. To this aim, fetal testes from human at 6.5-10.5 gestational weeks (GW) or from rat and mouse at a comparable critical period of development (14.5 days post-coitum (dpc) for rat and 12.5 dpc for mouse) were explanted and cultured using our validated organotypic culture system in the presence or absence of BPA for 1-3 days. BPA concentrations as low as 10(-8) M reduced testosterone secretion by human testes from day 1 of culture onwards, but not by mouse and rat testes where concentrations equal to 10(-5) M BPA were required. Similarly, 10(-8) M BPA reduced INSL3 mRNA levels only in human cultured testes. On the contrary, 10(-5) and 10(-6) M diethylstilbestrol (DES), a classical estrogenic compound, affected testosterone secretion only in rat and mouse testis cultures, but not in human testis cultures. Lastly, contrarily to the DES effect, the negative effect of BPA on testosterone produced by the mouse fetal testis was maintained after invalidation of estrogen receptor α (ERα). In conclusion, these results evidenced i) a deleterious effect of BPA on fetal Leydig cells function in human for concentrations from 10(-8) M upwards, ii) species-specific differences raising concerns about extrapolation of data from rodent studies to human risk assessment, iii) a specific signaling pathway for BPA which differs from the DES one and which does not involve ERα.", "link"=>"http://www.mendeley.com/research/differential-effects-bisphenol-diethylstilbestrol-human-rat-mouse-fetal-leydig-cell-function-4", "reader_count"=>48, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>2, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>4, "Other"=>6, "Student > Master"=>7, "Student > Bachelor"=>7, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>2, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>4, "Other"=>6, "Student > Master"=>7, "Student > Bachelor"=>7, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Environmental Science"=>4, "Biochemistry, Genetics and Molecular Biology"=>5, "Materials Science"=>1, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>8, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>3, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Chemistry"=>{"Chemistry"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"United States"=>1, "Israel"=>1, "France"=>2, "India"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/523299"], "description"=>"<p>Histological sections of human, rat and mouse fetal testes removed at 11 gestational week (GW), 14.5 day post conception (dpc) and 12.5 dpc respectively after one day of culture in control medium (D0) followed by 3 days of culture in the absence (control) or presence (BPA) of 10<sup>−5</sup> M BPA. At the end of the culture, testes were fixed in Bouin’s fluid and hematoxylin/eosin staining of the histological sections was performed. The testicular architecture and morphology were not affected by BPA-treatment. Black arrows: Sertoli cells; white arrows: Leydig cells; arrowhead: gonocytes.</p>", "links"=>[], "tags"=>["bpa", "testicular"], "article_id"=>193771, "categories"=>["Chemistry", "Biochemistry", "Cancer", "Cell Biology", "Physiology"], "users"=>["Thierry N’Tumba-Byn", "Delphine Moison", "Marlène Lacroix", "Charlotte Lecureuil", "Laëtitia Lesage", "Sophie M. Prud’homme", "Stéphanie Pozzi-Gaudin", "René Frydman", "Alexandra Benachi", "Gabriel Livera", "Virginie Rouiller-Fabre", "René Habert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0051579.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_BPA_treatment_on_testicular_histology_/193771", "title"=>"Effect of BPA treatment on testicular histology.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:31:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/523517"], "description"=>"<p>One testis per fetus (between 6.5 and 10.5 gestational week) was cut in different pieces that were cultured as separated explants in different wells (4 to 12 wells according to the age of the fetus). After 24 h of culture in control medium (D0), half of the explants were cultured in the absence (control) and the other half in the presence of BPA at concentrations ranging from 10<sup>−12</sup> M to 10<sup>−5</sup> M for 3 days (D1 to D3). The daily testosterone secretion in treated and untreated samples was measured by radioimmunoassay and the values at D1 to D3 were normalized to the D0 secretion of the same well. The D1 to D3 mean normalized secretion of treated samples are expressed as the percentage of that of the controls (untreated samples). Means ± SEM of these percentages from n fetuses are presented. n = 5 for 10<sup>−12</sup> M BPA, n = 7−8 for the other BPA concentrations. *p<0.05, ** p<0.01 in the statistical comparison between BPA-treated and control testes using the the Wilcoxon’s non-parametric paired test.</p>", "links"=>[], "tags"=>["bpa", "testosterone", "secretion", "fetal"], "article_id"=>194000, "categories"=>["Chemistry", "Biochemistry", "Cancer", "Cell Biology", "Physiology"], "users"=>["Thierry N’Tumba-Byn", "Delphine Moison", "Marlène Lacroix", "Charlotte Lecureuil", "Laëtitia Lesage", "Sophie M. Prud’homme", "Stéphanie Pozzi-Gaudin", "René Frydman", "Alexandra Benachi", "Gabriel Livera", "Virginie Rouiller-Fabre", "René Habert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0051579.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_BPA_on_testosterone_secretion_by_human_fetal_testes_/194000", "title"=>"Effect of BPA on testosterone secretion by human fetal testes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:32:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/523640"], "description"=>"<p>Individual (normalized to D0 and expressed as the percentage of the control explants) values at D2 of culture for the samples of the experiment described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051579#pone-0051579-g002\" target=\"_blank\">Figure 2</a> are presented. GW: gestational week.</p>", "links"=>[], "tags"=>["bpa", "testosterone", "secretion", "fetal", "testes"], "article_id"=>194117, "categories"=>["Chemistry", "Biochemistry", "Cancer", "Cell Biology", "Physiology"], "users"=>["Thierry N’Tumba-Byn", "Delphine Moison", "Marlène Lacroix", "Charlotte Lecureuil", "Laëtitia Lesage", "Sophie M. Prud’homme", "Stéphanie Pozzi-Gaudin", "René Frydman", "Alexandra Benachi", "Gabriel Livera", "Virginie Rouiller-Fabre", "René Habert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0051579.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_BPA_on_testosterone_secretion_by_human_fetal_testes_as_a_function_of_their_developmental_stage_/194117", "title"=>"Effect of BPA on testosterone secretion by human fetal testes as a function of their developmental stage.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:33:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/523748"], "description"=>"<p>Testes were removed from 14.5 dpc rat and 12.5 dpc mouse fetuses and cultured for one day in control medium (D0). Then, for each fetus, one testis was kept in control medium and the other one in medium supplemented with various concentrations of BPA as indicated for 3 days (D1 to D3). Values were calculated and expressed as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051579#pone-0051579-g001\" target=\"_blank\">Figure 1</a>; Rat: n = 9 for 10<sup>−12</sup> M, n = 12 for 10<sup>−8</sup> M, n = 9 for 10<sup>−7</sup> M, and n = 7 for 10<sup>−5</sup> M. Mouse: n = 9 for 10<sup>−12</sup> M, n = 15 for 10<sup>−8</sup> M, n = 17 for 10<sup>−7</sup> M and n = 10 for 10<sup>−5</sup> M. *p<0.05, ** p<0.01, *** p<0.001 in the statistical comparison between BPA-treated and control testes using the Wilcoxon’s non-parametric paired test.</p>", "links"=>[], "tags"=>["bpa", "testosterone", "secretion", "fetal"], "article_id"=>194229, "categories"=>["Chemistry", "Biochemistry", "Cancer", "Cell Biology", "Physiology"], "users"=>["Thierry N’Tumba-Byn", "Delphine Moison", "Marlène Lacroix", "Charlotte Lecureuil", "Laëtitia Lesage", "Sophie M. Prud’homme", "Stéphanie Pozzi-Gaudin", "René Frydman", "Alexandra Benachi", "Gabriel Livera", "Virginie Rouiller-Fabre", "René Habert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0051579.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_BPA_on_testosterone_secretion_by_rat_and_mouse_fetal_testes_/194229", "title"=>"Effect of BPA on testosterone secretion by rat and mouse fetal testes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:33:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/523847"], "description"=>"<p>Testes were removed from human fetuses at 6.5 to 10.5 weeks of gestation or from mouse and rat fetuses at 12.5 and 14.5 dpc, respectively. For each fetus, both testes were cultured in control medium for 24 h (D0) and then one in the presence of 10<sup>−8</sup> M BPA and the other one without for another 24 h. At the end of the culture, RT-PCR amplification was performed. Values are the mean ± SEM of <i>INSL3</i> mRNA level normalized to β-Actin one, and expressed as percentage of control values from 7 (human), 5 (mouse) and 6 (rat) independent experiments. * p<0.05 in the statistical comparison between BPA-treated and control testes using the paired Wilcoxon’s non-parametric paired test.</p>", "links"=>[], "tags"=>["bpa", "mrna", "fetal"], "article_id"=>194332, "categories"=>["Chemistry", "Biochemistry", "Cancer", "Cell Biology", "Physiology"], "users"=>["Thierry N’Tumba-Byn", "Delphine Moison", "Marlène Lacroix", "Charlotte Lecureuil", "Laëtitia Lesage", "Sophie M. Prud’homme", "Stéphanie Pozzi-Gaudin", "René Frydman", "Alexandra Benachi", "Gabriel Livera", "Virginie Rouiller-Fabre", "René Habert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0051579.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_10_8722_8_M_BPA_on_INSL3_mRNA_level_in_human_mouse_and_rat_fetal_testes_/194332", "title"=>"Effect of 10<sup>−8</sup> M BPA on <i>INSL3</i> mRNA level in human, mouse and rat fetal testes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:34:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/523920"], "description"=>"<p>Testes were removed from human fetuses at 6.5 to 10.5 weeks of gestation or from mouse and rat fetuses at 12.5 and 14.5 dpc, respectively. Like for the experiments presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051579#pone-0051579-g001\" target=\"_blank\">Figures 1</a> to <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0051579#pone-0051579-g003\" target=\"_blank\">3</a>, human rat and mouse testis explants were cultured in control medium (D0) for 24 h and then in the absence or presence of DES at 10<sup>−6</sup> M or 10<sup>−5</sup> M for the three subsequent days (D1–D3). Testosterone secretion in both treated and untreated samples at D1 to D3 was normalized to the D0 secretion of the same sample. The figure presents mean ± SEM of the D1 to D3 normalized values of treated samples expressed as the percentage of the control (untreated samples) values; n = 6, n = 7–10 and n = 7 for human, rat and mouse testes respectively. *p<0.05, ** p<0.01, *** p<0.001 in the statistical comparison between DES-treated and control testes using the Wilcoxon’s non-parametric paired test.</p>", "links"=>[], "tags"=>["des", "testosterone", "secretion", "fetal"], "article_id"=>194406, "categories"=>["Chemistry", "Biochemistry", "Cancer", "Cell Biology", "Physiology"], "users"=>["Thierry N’Tumba-Byn", "Delphine Moison", "Marlène Lacroix", "Charlotte Lecureuil", "Laëtitia Lesage", "Sophie M. Prud’homme", "Stéphanie Pozzi-Gaudin", "René Frydman", "Alexandra Benachi", "Gabriel Livera", "Virginie Rouiller-Fabre", "René Habert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0051579.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_DES_on_testosterone_secretion_by_human_rat_and_mouse_fetal_testes_/194406", "title"=>"Effect of DES on testosterone secretion by human, rat and mouse fetal testes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:34:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/523991"], "description"=>"<p>Testes from homozygous 12.5 dpc (ERα−/−), heterozygous (ERα+/−) and wild-type (ERα+/+) ERα-deficient fetuses were cultured on floating filters for 48 h. One testis from each animal was cultured in control medium and the other one in medium containing 10<sup>−5</sup> M BPA. Values are means ± SEM of testosterone secreted in the medium during the 2 days of culture by BPA-treated testes referred to testosterone secreted by the respective contralateral control testes; n = 6 (ERα+/+), 13 (ERα+/−) and 5 (ERα−/−), * p<0.05 in the statistical comparison between BPA-treated and control testes using the Wilcoxon’s parametric paired t test.</p>", "links"=>[], "tags"=>["inactivation", "testicular"], "article_id"=>194476, "categories"=>["Chemistry", "Biochemistry", "Cancer", "Cell Biology", "Physiology"], "users"=>["Thierry N’Tumba-Byn", "Delphine Moison", "Marlène Lacroix", "Charlotte Lecureuil", "Laëtitia Lesage", "Sophie M. Prud’homme", "Stéphanie Pozzi-Gaudin", "René Frydman", "Alexandra Benachi", "Gabriel Livera", "Virginie Rouiller-Fabre", "René Habert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0051579.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_ER_gene_inactivation_on_in_vitro_testicular_response_to_BPA_/194476", "title"=>"Effect of ERα gene inactivation on <i>in vitro</i> testicular response to BPA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:35:00"}

PMC Usage Stats | Further Information

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Relative Metric

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