PFOS exposure destroys the integrity of the blood-testis barrier (BTB) through PI3K/AKT/mTOR-mediated autophagy.
Reprod Biol
; 24(1): 100846, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38160586
ABSTRACT
Perfluorooctanesulfonate or perfluorooctane sulfonic acid (PFOS), a type of perfluorinated compound, is mainly found in consumer products. Exposure to PFOS could cause male reproductive toxicity by causing injury to the blood-testis barrier (BTB). However, the specific mechanisms through which PFOS affects male reproduction remain unclear. The mammalian target of rapamycin (mTOR) is a vital protein kinase that is believed to be a central regulator of autophagy. In this study, we established in vivo and in vitro models to explore the effects of PFOS on the BTB, autophagy, and the regulatory role of the mTOR signaling pathway. Adult mice were developmentally exposed to 0, 0.5, 5, and 10 mg/kg/day PFOS for five weeks. Thereafter, their testicular morphology, sperm counts, serum testosterone, expression of BTB-related proteins, and autophagy-related proteins were evaluated. Additionally, TM4 cells (a mouse Sertoli cell line) were used to delineate the molecular mechanisms that mediate the effects of PFOS on BTB. Our results demonstrated that exposure to PFOS induced BTB injury and autophagy, as evidenced by increased expression of autophagy-related proteins, accumulation of autophagosomes, observed through representative electron micrographs, and decreased activity of the PI3K/AKT/mTOR pathway. Moreover, treatment with chloroquine, an autophagy inhibitor, alleviated the effects of PFOS on the integrity of TM4 cells in the BTB and the PI3K/AKT/mTOR pathway. Overall, this study highlights that exposure to PFOS destroys the integrity of the BTB through PI3K/AKT/mTOR-mediated autophagy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Células de Sertoli
/
Ácidos Alcanossulfônicos
/
Proteínas Proto-Oncogênicas c-akt
/
Fluorocarbonos
Limite:
Animals
Idioma:
En
Revista:
Reprod Biol
Assunto da revista:
MEDICINA REPRODUTIVA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China