Effect of 4-nonylphenol (4-NP) on sperm function: Insights into the PI3K/PDK1/AKT signaling pathway during capacitation.
Reprod Toxicol
; 124: 108545, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38246476
ABSTRACT
4-Nonylphenol (4-NP) is an endocrine-disrupting chemical that impairs animal and human reproduction. However, the mechanisms underlying male reproductive dysfunction by 4-NP have not been fully understood. Herein, we demonstrated the effects of 4-NP on boar sperm functions and molecular mechanisms. Spermatozoa were treated with various concentrations of 4-NP (0, 10, 25, 50, 75, and 100 µM) during capacitation. Then, we evaluated sperm motility, capacitation status, intracellular ATP level, and cell viability. Finally, we measured the expression of phosphorylated protein kinase A (PKA), tyrosine phosphorylation, and proteins related to the phosphatidylinositol 3 kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (AKT) signaling pathways following exposure to 4-NP. Sperm motility and motion kinematics were reduced by 4-NP, whereas intracellular ATP levels were increased significantly in a dose-dependent manner. Furthermore, the expression levels of p-PI3K, PTEN, p-PDK1, AKT, and p-AKT exhibited a significant dose-dependent increase. Moreover, abnormal activation of PKA and tyrosine phosphorylation were observed. Specifically, the â¼24 kDa p-PKA substrate demonstrated a significant reduction following exposure to 4-Np. In addition, the â¼18 kDa p-PKA substrate and tyrosine-phosphorylated proteins displayed a significant dose-dependent increase after exposure to 4-NP. Our results suggest that 4-NP may induce detrimental effects on sperm functions through abnormal changes in PKA activity and tyrosine phosphorylation during capacitation, possibly through unusual alteration of the PI3K/PDK1/AKT signaling pathway. Therefore, 4-NP must be cautiously used considering its reproductive toxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenóis
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Fosfatidilinositol 3-Quinases
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Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Reprod Toxicol
Ano de publicação:
2024
Tipo de documento:
Article