The interference of DEHP in precocious puberty of females mediated by the hypothalamic IGF-1/PI3K/Akt/mTOR signaling pathway.
Ecotoxicol Environ Saf
; 181: 362-369, 2019 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-31212184
ABSTRACT
DEHP is reported to cause precocious puberty of females in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of sexual precocity. Prepubertal female rats were treated with DEHP for 4 weeks. Key organs were analyzed in control conditions and after exposure to 0.2, 1, and 5â¯mg/kg/day DEHP in pubertal female rats. To determine the role of the IGF-1/PI3K/Akt/mTOR signaling pathway in DEHP-induced female precocious puberty, 36 rats were treated with 5â¯mg/kg/day DEHP to establish a model of female precocious puberty. And we investigated the expression of genes and proteins related to IGF-1 pathway in rat hypothalamus after treatment with inhibitors. In the present study, we observed that DEHP treatment resulted in earlier vaginal opening time, higher number of Nissl bodies in the hypothalamus neurons, lower apoptosis of hypothalamic cells, higher IGF-1 and GnRH levels in the serum and hypothalamus. DEHP could also upregulated the expression of IGF-1/PI3K/Akt/mTOR pathway and GnRH in the hypothalamus of adolescent female rats, and inhibition of IGF-1R and mTOR in hypothalamus could block the activation of Kiss-1, GPR54, and GnRH by DEHP. In summary, our study suggested that DEHP might activate the hypothalamic GnRH neurons prematurely through the IGF-1 signaling pathway and promote GnRH release, leading to the initiation of female sexual development. Our results provide a new molecular mechanism underlying reproductive and developmental toxicity in pubertal female rats induced by DEHP.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pubertad Precoz
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Transducción de Señal
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Dietilhexil Ftalato
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Hipotálamo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article