Aquatic Toxicology 134–135 (2013) 104–111 Contents lists available at SciVerse ScienceDirect Aquatic Toxicology jou rn al hom epage: www.elsevier.com/locate/aquatox Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on reproduction in adult zebrafish (Danio rerio) Xiaoshan Liu a , Kyunghee Ji a,b , Areum Jo a , Hyo-Bang Moon c , Kyungho Choi a,∗ a Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul 151-742, Republic of Korea b Department of Biomedical Veterinary Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada c College of Science and Technology, Hanyang University, Ansan 426-791, Republic of Korea a r t i c l e i n f o Article history: Received 5 November 2012 Received in revised form 13 March 2013 Accepted 14 March 2013 Keywords: Organophosphate flame retardants Sex steroid VTG Reproduction Hypothalamus–pituitary–gonad axis a b s t r a c t 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-estradiol (E2) concentra- tions, 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 ˛ (ER˛), ER2 ˇ1, and follicle stim- ulating hormone ˇ (FSHˇ) were upregulated in the brain, while luteinizing hormone ˇ (LHˇ) and androgen receptor (AR) were downregulated. Corresponding to the upregulation of FSHˇ and downregulation of LHˇ 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 17ˇ-hydroxysteroid dehydrogenase (17ˇHSD) decreased, while transcription of CYP11A, CYP17, and CYP19A increased. In female fish, transcription ofGnRH2 and GnRHR3 decreased, but FSHˇ, LHˇ, CYP19B, ER˛, ER2ˇ1, 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 reg- ulatory mechanisms of the HPG axis, eventually leading to disruption of reproductive performance in fish. © 2013 Elsevier B.V. All rights reserved. Abbreviations: AR, androgen receptor; CYP11A, cytochrome P450 side-chain cleavage; 3HSD, 3-hydroxysteroid dehydrogenase; CYP17, cytochrome P450 17; 17HSD, 17-hydroxysteroid dehydrogenase; CYP19, cytochrome P450 19; Ct, threshold cycle; DMSO, dimethyl sulfoxide; E2, 17-estradiol; ER, estrogen receptor; FSH, follicle stimulating hormone ; FSHR, follicle stimulating hormone receptor; GnRH, gonadotropin-releasing hormone; GnRHR, gonadotropin-releasing hormone receptor; HMGR, hydroxymethylglutaryl CoA reductase; LH, luteinizing hormone ; LHR, luteinizing hormone receptor; FSH, follicle stimulating hormone ; FSHR, follicle stimulating hormone receptor; StAR, steroidogenic acute regulatory protein; T, testosterone; 11-KT, 11-ketotestosterone. ∗ Corresponding author at: School of Public Health, Seoul National University, 1 Gwanakro, Gwanak, Seoul 151-742, Republic of Korea. Tel.: +82 2 880 2738; fax: +82 2 745 9104. E-mail address: kyungho@snu.ac.kr (K. Choi). 1. Introduction Due to the phase-out of major commercial polybrominated diphenyl ether (PBDE) mixtures, such as pentaBDE and octaBDE products, and more recently decaBDE, from the markets of USA and Europe since 2003 (Covaci et al., 2011), the production and use of alternative flame retardants (FRs), such as organophos- phate flame retardants (OPFRs), have increased (Reemtsma et al., 2008). Among the OPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP) and triphenyl phosphate (TPP) have been widely used in polyurethane foams since 1970s, which are commonly found in sofas, chairs, and car upholstery (Marklund et al., 2003; Reemtsma et al., 2008; Stapleton et al., 2009). These chemicals have also been detected in effluents from German sewage treatment plants (STPs), 0166-445X/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.aquatox.2013.03.013