Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring.
Ecotoxicol Environ Saf
; 270: 115941, 2024 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-38184977
ABSTRACT
Early exposure to dibutyl phthalate (DBP) can cause hypospadias in newborn foetuses. However, the underlying molecular mechanism is not well defined. Aberrant angiogenesis is associated with various dysplasias including urogenital deficits. In vivo and in vitro angiogenesis assays showed reduced angiogenesis in the hypospadias group and DBP exposed group. RNA-sequencing analysis of DBP-treated HUVECs revealed decreased expression of transforming growth factor beta 1-induced transcript 1 (TGFB1I1) and a significantly enriched angiogenesis-associated pathway. Further experiments revealed that decreased TGFB1I1 expression was associated with disrupted tube formation and migration, which resulted in decreased angiogenesis. Functional assays revealed that the overexpression of TGFB1I1 promoted tube formation and migration of HUVECs in the DBP-treated group. Moreover, we showed that the transcription factor AR was regulated by TGFB1I1 through inhibiting its translocation from the cytoplasm to the nucleus. Together, our results identified TGFB1I1 as a component of aberrant angiogenesis in hypospadias rats and its interaction with AR might be a potential target for hypospadias development.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dibutilftalato
/
Hipospadia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Ecotoxicol Environ Saf
Ano de publicação:
2024
Tipo de documento:
Article