Reduced Fgf10/Fgfr2 and androgen receptor (AR) in anorectal malformations male rats induced by di-n-butyl phthalate (DBP): A study on the local and systemic toxicology of DBP
- PMID: 26514922
- DOI: 10.1016/j.tox.2015.10.006
Reduced Fgf10/Fgfr2 and androgen receptor (AR) in anorectal malformations male rats induced by di-n-butyl phthalate (DBP): A study on the local and systemic toxicology of DBP
Abstract
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 Fgf10/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 Fgf10/Fgfr2 signaling and AR in pathogenesis of local and systemic development defects in ARMs male rats induce by DBP.
Keywords: Androgen receptor; Anorectal malformations; Di-n-butyl phthalate; Fibroblast growth factor 10; Fibroblast growth factor receptor 2; Multiple organs.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Similar articles
-
Potential involvement of Fgf10/Fgfr2 and androgen receptor (AR) in renal fibrosis in adult male rat offspring subjected to prenatal exposure to di-n-butyl phthalate (DBP).Toxicol Lett. 2018 Jan 5;282:37-42. doi: 10.1016/j.toxlet.2017.09.009. Epub 2017 Sep 15. Toxicol Lett. 2018. PMID: 28919491
-
Maternal exposure to di-n-butyl phthalate (DBP) induces combined anorectal and urogenital malformations in male rat offspring.Reprod Toxicol. 2016 Jun;61:169-76. doi: 10.1016/j.reprotox.2016.04.007. Epub 2016 Apr 11. Reprod Toxicol. 2016. PMID: 27079746
-
Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate.Environ Toxicol. 2016 Mar;31(3):261-8. doi: 10.1002/tox.22040. Epub 2014 Sep 12. Environ Toxicol. 2016. PMID: 25213187
-
Genetic and nongenetic etiology of nonsyndromic anorectal malformations: a systematic review.Birth Defects Res C Embryo Today. 2014 Dec;102(4):382-400. doi: 10.1002/bdrc.21068. Birth Defects Res C Embryo Today. 2014. PMID: 25546370 Review.
-
Anorectal malformation: the etiological factors.Pediatr Surg Int. 2015 Sep;31(9):795-804. doi: 10.1007/s00383-015-3685-0. Epub 2015 Apr 22. Pediatr Surg Int. 2015. PMID: 25899933 Review.
Cited by
-
2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.J Oncol. 2021 Apr 30;2021:9955456. doi: 10.1155/2021/9955456. eCollection 2021. J Oncol. 2021. PMID: 34007277 Free PMC article. Review.
-
Maternal exposure to di-n-butyl phthalate (DBP) induces renal fibrosis in adult rat offspring.Oncotarget. 2017 May 9;8(19):31101-31111. doi: 10.18632/oncotarget.16088. Oncotarget. 2017. PMID: 28415704 Free PMC article.
-
Perinatal exposures to phthalates and phthalate mixtures result in sex-specific effects on body weight, organ weights and intracisternal A-particle (IAP) DNA methylation in weanling mice.J Dev Orig Health Dis. 2019 Apr;10(2):176-187. doi: 10.1017/S2040174418000430. Epub 2018 Jul 11. J Dev Orig Health Dis. 2019. PMID: 29991372 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous