Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats
Administration of dibutyl phthalate (DBP) to pregnant rats causes reproductive disorders in male offspring, resulting from suppression of intratesticular testosterone, and is used as a model for human testicular dysgenesis syndrome (TDS). DBP exposure in pregnancy induces focal dysgenetic areas in f...
| Autor principal: | Lara, Nathália L.M. |
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| Outros Autores: | van den Driesche, Sander, MacPherson, Sheila A., França, Luiz Renato de, Sharpe, Richard M. |
| Grau: | Artigo |
| Idioma: | English |
| Publicado em: |
Scientific Reports
2020
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| Acesso em linha: |
https://repositorio.inpa.gov.br/handle/1/15217 |
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oai:repositorio:1-15217 |
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oai:repositorio:1-15217 Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats Lara, Nathália L.M. van den Driesche, Sander MacPherson, Sheila A. França, Luiz Renato de Sharpe, Richard M. Phthalic Acid Dibutyl Ester Animals Chemically Induced Disease Model Drug Effect Female Fetus Gonadal Dysgenesis Growth, Development And Aging Human Leydig Cell Male Pathology Pathophysiology Pregnancy Prenatal Exposure Rat Seminiferous Tubule Sex Differentiation Testis Testis Disease Wistar Rat Animal Dibutyl Phthalate Disease Models, Animals Female Fetus Gonadal Dysgenesis Humans Leydig Cells Male Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Seminiferous Tubules Sex Differentiation Testicular Diseases Testis Administration of dibutyl phthalate (DBP) to pregnant rats causes reproductive disorders in male offspring, resulting from suppression of intratesticular testosterone, and is used as a model for human testicular dysgenesis syndrome (TDS). DBP exposure in pregnancy induces focal dysgenetic areas in fetal testes that appear between e19.5-e21.5, manifesting as focal aggregation of Leydig cells and ectopic Sertoli cells (SC). Our aim was to identify the origins of the ectopic SC. Time-mated female rats were administered 750 mg/kg/day DBP in three different time windows: full window (FW; e13.5-e20.5), masculinisation programming window (MPW; e15.5-e18.5), late window (LW; e19.5-e20.5). We show that DBP-MPW treatment produces more extensive and severe dysgenetic areas, with more ectopic SC and germ cells (GC) than DBP-FW treatment; DBP-LW induces no dysgenesis. Our findings demonstrate that ectopic SC do not differentiate de novo, but result from rupture of normally formed seminiferous cords beyond e20.5. The more severe testis dysgenesis in DBP-MPW animals may result from the presence of basally migrating GC and a weakened basal lamina, whereas GC migration was minimal in DBP-FW animals. Our findings provide the first evidence for how testicular dysgenesis can result after normal testis differentiation/development and may be relevant to understanding TDS in human patients. © 2017 The Author(s). 2020-05-07T14:14:46Z 2020-05-07T14:14:46Z 2017 Artigo https://repositorio.inpa.gov.br/handle/1/15217 10.1038/s41598-017-02684-2 en Volume 7, Número 1 Attribution-NonCommercial-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nc-nd/3.0/br/ application/pdf Scientific Reports |
| institution |
Instituto Nacional de Pesquisas da Amazônia - Repositório Institucional |
| collection |
INPA-RI |
| language |
English |
| topic |
Phthalic Acid Dibutyl Ester Animals Chemically Induced Disease Model Drug Effect Female Fetus Gonadal Dysgenesis Growth, Development And Aging Human Leydig Cell Male Pathology Pathophysiology Pregnancy Prenatal Exposure Rat Seminiferous Tubule Sex Differentiation Testis Testis Disease Wistar Rat Animal Dibutyl Phthalate Disease Models, Animals Female Fetus Gonadal Dysgenesis Humans Leydig Cells Male Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Seminiferous Tubules Sex Differentiation Testicular Diseases Testis |
| spellingShingle |
Phthalic Acid Dibutyl Ester Animals Chemically Induced Disease Model Drug Effect Female Fetus Gonadal Dysgenesis Growth, Development And Aging Human Leydig Cell Male Pathology Pathophysiology Pregnancy Prenatal Exposure Rat Seminiferous Tubule Sex Differentiation Testis Testis Disease Wistar Rat Animal Dibutyl Phthalate Disease Models, Animals Female Fetus Gonadal Dysgenesis Humans Leydig Cells Male Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Seminiferous Tubules Sex Differentiation Testicular Diseases Testis Lara, Nathália L.M. Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats |
| topic_facet |
Phthalic Acid Dibutyl Ester Animals Chemically Induced Disease Model Drug Effect Female Fetus Gonadal Dysgenesis Growth, Development And Aging Human Leydig Cell Male Pathology Pathophysiology Pregnancy Prenatal Exposure Rat Seminiferous Tubule Sex Differentiation Testis Testis Disease Wistar Rat Animal Dibutyl Phthalate Disease Models, Animals Female Fetus Gonadal Dysgenesis Humans Leydig Cells Male Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Seminiferous Tubules Sex Differentiation Testicular Diseases Testis |
| description |
Administration of dibutyl phthalate (DBP) to pregnant rats causes reproductive disorders in male offspring, resulting from suppression of intratesticular testosterone, and is used as a model for human testicular dysgenesis syndrome (TDS). DBP exposure in pregnancy induces focal dysgenetic areas in fetal testes that appear between e19.5-e21.5, manifesting as focal aggregation of Leydig cells and ectopic Sertoli cells (SC). Our aim was to identify the origins of the ectopic SC. Time-mated female rats were administered 750 mg/kg/day DBP in three different time windows: full window (FW; e13.5-e20.5), masculinisation programming window (MPW; e15.5-e18.5), late window (LW; e19.5-e20.5). We show that DBP-MPW treatment produces more extensive and severe dysgenetic areas, with more ectopic SC and germ cells (GC) than DBP-FW treatment; DBP-LW induces no dysgenesis. Our findings demonstrate that ectopic SC do not differentiate de novo, but result from rupture of normally formed seminiferous cords beyond e20.5. The more severe testis dysgenesis in DBP-MPW animals may result from the presence of basally migrating GC and a weakened basal lamina, whereas GC migration was minimal in DBP-FW animals. Our findings provide the first evidence for how testicular dysgenesis can result after normal testis differentiation/development and may be relevant to understanding TDS in human patients. © 2017 The Author(s). |
| format |
Artigo |
| author |
Lara, Nathália L.M. |
| author2 |
van den Driesche, Sander MacPherson, Sheila A. França, Luiz Renato de Sharpe, Richard M. |
| author2Str |
van den Driesche, Sander MacPherson, Sheila A. França, Luiz Renato de Sharpe, Richard M. |
| title |
Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats |
| title_short |
Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats |
| title_full |
Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats |
| title_fullStr |
Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats |
| title_full_unstemmed |
Dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats |
| title_sort |
dibutyl phthalate induced testicular dysgenesis originates after seminiferous cord formation in rats |
| publisher |
Scientific Reports |
| publishDate |
2020 |
| url |
https://repositorio.inpa.gov.br/handle/1/15217 |
| _version_ |
1787143914207051776 |
| score |
11.755432 |