title: Exposure to DEHP and MEHP from hatching to adulthood causes reproductive dysfunction and endocrine disruption in marine medaka (Oryzias melastigma).
abstract: Concern has increased regarding the adverse effects of di-(2-ethylhexyl)-phthalate (DEHP) on reproduction. However, limited information is available on the effects of DEHP in marine organisms. The aim of the present study was to examine whether long-term exposure to DEHP and its active metabolite mono-(2-ethylhexyl)-phthalate (MEHP) disrupts endocrine function in marine medaka (Oryzias melastigma). Marine medaka larvae were exposed to either DEHP (0.1 and 0.5mg/L) or MEHP (0.1 and 0.5mg/L) for 6 months, and the effects on reproduction, sex steroid hormones, liver vitellogenin (VTG), gonad histology and the expression of genes involved in the hypothalamic-pituitary-gonad (HPG) axis were investigated. Exposure to DEHP, but not MEHP, from hatching to adulthood accelerated the start of spawning and decreased the egg production of exposed females. Moreover, exposure to both DEHP and MEHP resulted in a reduction in the fertilization rate of oocytes spawned by untreated females paired with treated males. A significant increase in plasma 17β-estradiol (E2) along with a significant decrease in testosterone (T)/E2 ratios was observed in males, which was accompanied by the upregulation of ldlr, star, cyp17a1, 17βhsd, and cyp19a transcription in the testis. Increased concentrations of T and E2 were observed in females, which was consistent with the upregulation of ldlr. The expression of brain gnrhr2, fshβ, cyp19b and steroid hormone receptor genes also corresponded well with hormonal and reproductive changes. The liver VTG level was significantly increased after DEHP and MEHP exposure in males. DEHP induced histological changes in the testes and ovaries: the testes displayed a reduced number of spermatozoa, and the ovaries displayed an increased number of atretic follicles. In addition, the tissue concentrations of MEHP, MEHHP and MEOHP in DEHP-exposed groups were much higher than those in MEHP-exposed groups, and there were no dose- or sex-specific effects. Thus, DEHP exerts more obvious toxic effects compared with MEHP. There were some commonalities in the toxic effects and molecular mechanisms of DEHP and MEHP, suggesting that some of the toxic effects of DEHP may be induced by both DEHP itself and DEHP metabolites (including MEHP). Taken together, these results indicate that exposure to DEHP and MEHP from hatching to adulthood causes endocrine disruption with sex-specific effects in marine medaka, with males being more sensitive than females.
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Kang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China.
authors.forename: Qiansheng
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Shen
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China. Electronic address: sjdong@iue.ac.cn.
authors.forename: Sijun
authors.initials: S
authors.lastname: Dong
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects*; D004781:Environmental Exposure; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000378:metabolism; D006066:Gonads / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009990:Oryzias / Q000502:physiology*; D012098:Reproduction / Q000187:drug effects*; D014819:Vitellogenins / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D012739:Gonadal Steroid Hormones; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate
keywords: 17β-estradiol; BSI; CYP450 21-α-hydroxylase; DEHP; DMSO; E2; Endocrine disruption; GSI; HPG; Hypothalamic-pituitary-gonad (HPG) axis; K; MEHHP; MEHP; MEOHP; Oryzias melastigma; T; VTG; androgen receptor α; arα; brain somatic index; condition factor; cyp11b; cyp17a1; cyp19; cyp21a; cyp3a; cytochrome P450 11b; cytochrome P450 17α-hydroxylase 1; cytochrome P450 19; cytochrome P450 3a; di-(2-ethylhexyl)-phthalate; dimethyl sulfoxide; er; estrogen receptor; follicle-stimulating hormone; fsh; ghr; glucocorticoid receptor; gnrhr2; gonadal somatic index; gonadotropin-releasing hormone receptor 2; gr; growth hormone receptor; hsd; hydroxysteroid dehydrogenase; hypothalamic-pituitary-gonad; igf1r; insulin-like growth-factor-1 receptor; ldlr; low density lipoprotein receptor; mono-(2-ethyl-5-hydroxyhexyl)-phthalate; mono-(2-ethyl-5-oxohexyl)-phthalate; mono-(2-ethylhexyl)-phthalate; nr5a2; nuclear receptor subfamily-5 group a member 2; peroxisome proliferator-activated receptor; ppar; qRT-PCR; real-time quantitative reverse transcriptase polymerase chainreaction; star; steroidogenic acute regulatory protein; testosterone; vitellogenin