Chronic low-dose exposure of nonylphenol alters energy homeostasis in the reproductive system of female rats.
Toxicol Appl Pharmacol
; 348: 67-75, 2018 06 01.
Article
em En
| MEDLINE
| ID: mdl-29641977
ABSTRACT
Nonylphenol (NP) as a confirmed endocrine disrupt chemical that causes reproductive and developmental toxicity. Previous studies focused only on short-term, high-dose exposure in vivo, or in vitro on female reproductive toxicity, which cannot accurately simulate the real human exposure scenario. The present study aims to explore NP toxicity and the underlying mechanisms of chronic low-dose NP exposure (500⯵g/kg·bw/day, for 8â¯weeks) in the reproductive system of female rats. The results indicated that NP exposure caused female reproductive toxicity, including alterations in serum 17ß-estradiol (E2) levels, endometria hyperplasia, altered oogenesis and significant changes in the metabolic profile observed in urine, serum, uterus and ovary. Furthermore, expression of the energy-sensitive proteins carnitine palmitoyltransferase I (CPTI), adenosine 5'-monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma (PPAR-γ) were found to be down-regulated in uterus under NP exposure, which suggested the impaired fatty acid oxidation. Accordingly, a comprehensive metabolomics study in key reproductive tissues and body fluids revealed that 12 metabolites were associated with energy metabolism as potential biomarkers for the evaluation of low toxicity at early stages, with L-carnitines being the most representative ones. The present findings provide evidence that chronic low-dose NP exposure can significantly disrupt energy homeostasis in females, thus offering further insights into NP reproductive toxicity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ovário
/
Fenóis
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Reprodução
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Hiperplasia Endometrial
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Endométrio
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Metabolismo Energético
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Disruptores Endócrinos
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article