Impact of early exposure to DEHP phthalate on the expression and subcellular localization of the pituitary androgen receptor

Di-2-ethylhexyl phthalate (DEHP) is a human-made compound with disruptive effects on the endocrine system. It is used in a wide variety of daily products (plastics, diapers, cosmetics) and crosses the placental barrier, affecting fetal development. Its impact on the pituitary gland and pote...

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Detalles Bibliográficos
Autores principales: Pérez, PA, Silva, TY, Gomá , L, Toledo , J, Gutiérrez, S
Formato: Artículo revista
Lenguaje:Español
Publicado: Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2023
Materias:
DEHP
Androgen receptor
Pituitary
GONADOTROPH
receptor de andrógenos
ADENOHIPOFISIS
GONADOTROPAS
Acceso en línea:https://revistas.unc.edu.ar/index.php/med/article/view/42648
Aporte de:
Revista de la Facultad de Ciencias Médicas de Córdoba de Universidad Nacional de Córdoba
id I10-R327-article-42648
record_format ojs
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-327
container_title_str Revista de la Facultad de Ciencias Médicas de Córdoba
language Español
format Artículo revista
topic DEHP
Androgen receptor
Pituitary
GONADOTROPH
DEHP
receptor de andrógenos
ADENOHIPOFISIS
GONADOTROPAS
spellingShingle DEHP
Androgen receptor
Pituitary
GONADOTROPH
DEHP
receptor de andrógenos
ADENOHIPOFISIS
GONADOTROPAS
Pérez, PA
Silva, TY
Gomá , L
Toledo , J
Gutiérrez, S
Impact of early exposure to DEHP phthalate on the expression and subcellular localization of the pituitary androgen receptor
topic_facet DEHP
Androgen receptor
Pituitary
GONADOTROPH
DEHP
receptor de andrógenos
ADENOHIPOFISIS
GONADOTROPAS
author Pérez, PA
Silva, TY
Gomá , L
Toledo , J
Gutiérrez, S
author_facet Pérez, PA
Silva, TY
Gomá , L
Toledo , J
Gutiérrez, S
author_sort Pérez, PA
title Impact of early exposure to DEHP phthalate on the expression and subcellular localization of the pituitary androgen receptor
title_short Impact of early exposure to DEHP phthalate on the expression and subcellular localization of the pituitary androgen receptor
title_full Impact of early exposure to DEHP phthalate on the expression and subcellular localization of the pituitary androgen receptor
title_fullStr Impact of early exposure to DEHP phthalate on the expression and subcellular localization of the pituitary androgen receptor
title_full_unstemmed Impact of early exposure to DEHP phthalate on the expression and subcellular localization of the pituitary androgen receptor
title_sort impact of early exposure to dehp phthalate on the expression and subcellular localization of the pituitary androgen receptor
description Di-2-ethylhexyl phthalate (DEHP) is a human-made compound with disruptive effects on the endocrine system. It is used in a wide variety of daily products (plastics, diapers, cosmetics) and crosses the placental barrier, affecting fetal development. Its impact on the pituitary gland and potential molecular alterations are not fully understood. The aim of this study was to analyze whether DEHP exposure during development affects the expression and localization of the pituitary androgen receptor (AR) and its impact on the gonadotroph cell population. Pregnant rats (n=12) were randomly assigned to 2 groups: DEHP (200 µg/kg/day) and control (vehicle: corn oil), administered orally from gestation day 1 until weaning. Offspring (n=30 females and 30 males) were sacrificed on postnatal day (PND) 21 (prepubertal) or 75 (adults). The pituitary glands were processed for quantification of bLH-expressing cells (gonadotrophs) and AR by flow cytometry, for nuclear and cytoplasmic AR protein determination by western blot (WB), for identification of gonadotrophs (bLH+) and subcellular AR localization by immunofluorescence (IF). Statistical analysis was performed using ANOVA Tukey.  In males, DEHP significantly increased the percentage of AR+ cells both at PND21 and PND75. Interestingly, in females, the effect of DEHP was similar at PND21 but opposite at PND75. In both sexes, DEHP significantly increased cytoplasmic AR expression, with a decrease in nuclear immunostaining. Furthermore, it was determined that exposure to this phthalate induces a significant increase in the gonadotroph population in both males and females at PND21, while in adulthood, a significant decrease was observed only in exposed females, with no significant changes in males. These results demonstrate that DEHP exposure during development modifies the size of the gonadotroph population and alters the patterns of expression and subcellular localization of AR, suggesting that this phthalate affects pituitary androgenic signaling, exerting a differential effect on males and females.
publisher Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
publishDate 2023
url https://revistas.unc.edu.ar/index.php/med/article/view/42648
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spelling I10-R327-article-426482023-10-19T21:20:23Z Impact of early exposure to DEHP phthalate on the expression and subcellular localization of the pituitary androgen receptor Impacto de la exposición temprana al ftalato DEHP sobre la expresión y localización subcelular del receptor de andrógenos adenohipofisario Pérez, PA Silva, TY Gomá , L Toledo , J Gutiérrez, S DEHP Androgen receptor Pituitary GONADOTROPH DEHP receptor de andrógenos ADENOHIPOFISIS GONADOTROPAS Di-2-ethylhexyl phthalate (DEHP) is a human-made compound with disruptive effects on the endocrine system. It is used in a wide variety of daily products (plastics, diapers, cosmetics) and crosses the placental barrier, affecting fetal development. Its impact on the pituitary gland and potential molecular alterations are not fully understood. The aim of this study was to analyze whether DEHP exposure during development affects the expression and localization of the pituitary androgen receptor (AR) and its impact on the gonadotroph cell population. Pregnant rats (n=12) were randomly assigned to 2 groups: DEHP (200 µg/kg/day) and control (vehicle: corn oil), administered orally from gestation day 1 until weaning. Offspring (n=30 females and 30 males) were sacrificed on postnatal day (PND) 21 (prepubertal) or 75 (adults). The pituitary glands were processed for quantification of bLH-expressing cells (gonadotrophs) and AR by flow cytometry, for nuclear and cytoplasmic AR protein determination by western blot (WB), for identification of gonadotrophs (bLH+) and subcellular AR localization by immunofluorescence (IF). Statistical analysis was performed using ANOVA Tukey.  In males, DEHP significantly increased the percentage of AR+ cells both at PND21 and PND75. Interestingly, in females, the effect of DEHP was similar at PND21 but opposite at PND75. In both sexes, DEHP significantly increased cytoplasmic AR expression, with a decrease in nuclear immunostaining. Furthermore, it was determined that exposure to this phthalate induces a significant increase in the gonadotroph population in both males and females at PND21, while in adulthood, a significant decrease was observed only in exposed females, with no significant changes in males. These results demonstrate that DEHP exposure during development modifies the size of the gonadotroph population and alters the patterns of expression and subcellular localization of AR, suggesting that this phthalate affects pituitary androgenic signaling, exerting a differential effect on males and females. El ftalato di-2-etilhexilftalato (DEHP) es un compuesto antrópico con efectos disruptivos sobre el sistema endocrino, utilizado en una amplia variedad de productos de uso diario (plásticos, pañales, cosméticos), que atraviesa la barrera placentaria y afecta el desarrollo fetal. Su impacto sobre la hipófisis y las potenciales alteraciones moleculares no son completamente conocidas. El objetivo del presente trabajo fue analizar si la exposición a DEHP durante el desarrollo afecta la expresión y localización del receptor de andrógenos (AR) adenohipofisario y su impacto sobre la población de células gonadotropas. Ratas preñadas (n=12) fueron asignadas al azar a 2 grupos: DEHP (200 µg/kg/día) y control (vehículo: aceite de maíz), administrados oralmente desde el día 1 de gestación hasta el destete. Las crías (n= 30 hembra y 30 machos) fueron sacrificadas al día postnatal (PND) 21 (prepuberal) o 75 (adultos). Las adenohipófisis fueron procesadas para la cuantificación de las células que expresan bLH (gonadotropas) y AR por citometría de flujo, para la determinación proteica del AR en fracción nuclear y citoplasmática por western blot (WB), para la identificación de las gonadotropas (bLH+) y localización subcelular del AR por inmunofluorescencia (IF) Se realizó análisis estadístico ANOVA Tukey. En machos, DEHP incrementó significativamente el porcentaje de células AR+ tanto a los PND21 como a los PND75. Curiosamente en hembras el efecto de DEHP fue similar a PND21 pero opuesto a los PND75. En ambos sexos DEHP incrementó significativamente la expresión del AR citoplasmático, con disminución de la inmunomarcación nuclear. Además, se determinó que la exposición a este ftalato induce un incremento significativo de la población gonadotropa tanto en machos como hembras a los PND21, mientras que, en la edad adulta, se observó una disminución significativa solo en hembras expuestas, sin cambios significativos en machos. Estos resultados muestran que la exposición al DEHP durante el desarrollo modifica el tamaño de la población de gonadotropas y altera los patrones de expresión y localización subcelular del AR, sugiriendo que este ftalato afecta la señalización androgénica adenohipofisaria, ejerciendo un efecto diferencial en machos y hembras. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2023-10-19 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/42648 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 80 (2023): Suplemento JIC XXIV Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 80 (2023): Suplemento JIC XXIV Revista da Faculdade de Ciências Médicas de Córdoba; v. 80 (2023): Suplemento JIC XXIV 1853-0605 0014-6722 spa https://revistas.unc.edu.ar/index.php/med/article/view/42648/42853 Derechos de autor 2023 Universidad Nacional de Córdoba http://creativecommons.org/licenses/by-nc/4.0

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