期刊
TOXICOLOGY
卷 338, 期 -, 页码 77-85出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2015.10.006
关键词
Anorectal malformations; Di-n-butyl phthalate; Fibroblast growth factor 10; Fibroblast growth factor receptor 2; Androgen receptor; Multiple organs
资金
- National Natural Science Foundation of China [813700041]
- Foundation for National Clinical Key Subject Construction Project (Department of Urology, Shanghai First People's Hospital)
Previous study have demonstrated that not only the anorectal development but also the general conditions of anorectal malformations (ARMs) male rats are severely affected by di-n-butyl phthalate (DBP) maternal exposure. However, the mechanisms underlying DBP-induced congenital defects remain elusive. Reportedly, Fgf10/Fgfr2 and androgen receptor (AR) are pivotal for the development of multiple organs. In this study, we therefore investigated the expression of FgflO/Fgfr2 together with AR in the terminal rectum and multiple organs of ARM male rats induced by in utero exposure to DBP. DBP was administered to pregnant rats to establish the model and the incidence of ARMs in male offspring was 39.5%. On postnatal day(PND)1, the gross photograph and histopathological staining confirmed the abnormal manifestations in these organs of newborn ARMs. Decreased anogenital distance, body weight and serum testosterone level were observed in ARM male offspring. The reduced expression of Fgf10/Fgfr2 mRNA and protein was seen in terminal rectum and kidney, spleen, liver, heart in ARM male rats, whereas the reduced expression of AR was only observed in the kidney and terminal rectum. Our findings suggest the potential involvement of altered FgflO/Fgfr2 signaling and AR in pathogenesis of local and systemic development defects in ARMs male rats induce by DBP. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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