Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on reproduction in adult zebrafish (Danio rerio)

Abstract

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) belong to the group of triester organophosphate flame retardants (OPFRs), which have been used in a wide range of consumer products. These chemicals have been frequently detected in effluents, surface water, and fish, and hence their potential adverse effects on aquatic ecosystem are of concern. The present study was conducted to investigate the reproduction-related effects and possible molecular mechanisms of TDCPP and TPP using a 21 day reproduction test employing adult zebrafish (Danio rerio). After 21 d of exposure to TDCPP or TPP, significant decrease in fecundity along with significant increases of plasma 17 beta-estradiol (E2) concentrations, vitellogenin (VTG) levels, and E2/testosterone (T) and E2/11-ketotestosterone (11-KT) ratios were observed. The transcriptional profiles of several genes of the hypothalamus-pituitary-gonad (HPG) axis changed as well after the exposure, but the trend was sex-dependent. In male fish, gonadotropin-releasing hormone2 (GnRH2), GnRHR3, cytochrome P450 (CYP) 19B, estrogen receptor alpha (ER alpha), ER2 beta 1, and follicle stimulating hormone p (FSH beta) were upregulated in the brain, while luteinizing hormone beta (LH beta) and androgen receptor (AR) were downregulated. Corresponding to the upregulation of FSH beta and downregulation of LH beta in the brain, FSHR was upregulated and LHR was downregulated in the testis. Among the genes that regulate the steroidogenesis pathway, transcription of hydroxyl methyl glutaryl CoA reductase (HMGRA), steroidogenic acute regulatory protein (StAR), and 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) decreased, while transcription of CYP11A, CYP17, and CYP19A increased. In female fish, transcription of GnRH2 and GnRHR3 decreased, but FSH beta, LH beta, CYP19B, ER alpha, ER2 beta 1, and AR transcription increased in the brain. In the ovary, FSHR and LHR were significantly upregulated, and most steroidogenic genes were significantly upregulated. The observed disruption of GnRH and GtHs could be further related to subsequent disruption in both sex steroid hormone balance and plasma VTG levels, as well as reproductive performance. Overall, our observation indicates that both TDCPP and TPP could disturb the sex hormone balance by altering regulatory mechanisms of the HPG axis, eventually leading to disruption of reproductive performance in fish. (C) 2013 Elsevier B.V. All rights reserved.