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Toxicol Appl Pharmacol. 2018 Jun 1;348:67-75. doi: 10.1016/j.taap.2018.04.007. Epub 2018 Apr 8.

Chronic low-dose exposure of nonylphenol alters energy homeostasis in the reproductive system of female rats.

Author information

1
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
2
Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, 60 College Street, New Haven, CT 06520-8034, USA.
3
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China. Electronic address: q_xu68@163.com.
4
Laboratory Animal Center, Southeast University, Nanjing 210009, China. Electronic address: xb_w@163.com.

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 μg/kg·bw/day, for 8 weeks) in the reproductive system of female rats. The results indicated that NP exposure caused female reproductive toxicity, including alterations in serum 17β-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.

KEYWORDS:

CPTI/AMPK/mTOR/PPAR-γ; Chronic low-dose exposure; Energy homeostasis; Metabonomics; Nonylphenol; Reproductive toxicity

PMID:
29641977
DOI:
10.1016/j.taap.2018.04.007
[Indexed for MEDLINE]

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