title: Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations.
abstract: Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17beta-estradiol (E2), estrone (E1), estriol (E3), progesterone (P4) and 17alpha-ethynylestradiol (EE2)). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC50 values for a reduction in normal development was as follows: TBT(L. anamesus)>OCT>TBT(S. purpuratus)>>E2>EE2>DDD>>BisA>P4>E1>>E3. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E2, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at concentrations as low as 0.02 ng/ml and was effective at this concentration in decreasing the sensitivities of the embryos to estradiol and estrogenic EDCs. The complete antagonist ICI 182,780 inhibited development at concentrations as low as 0.03 ng/ml but increased embryo sensitivity to estradiol and estrogenic EDCs. Estradiol and estrogenic EDCs all cause developmental toxicity in sea urchins through a TAM-sensitive but an ICI-insensitive mechanism. It remains to be demonstrated whether this mechanism involves an estrogen-responsive nuclear receptor (NR), a membrane receptor (NR or non-NR-related) or a completely different mechanism of toxicity. However, early embryo sensitivity and the differential response to SERM co-incubation further suggests more than one mode of EDC action in the developing sea urchin embryo.
authors.affiliation: Bodega Marine Laboratory, University of California, Davis, POB 247, Bodega Bay, CA 94923, USA.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Roepke
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Snyder
authors.forename: Gary N
authors.initials: GN
authors.lastname: Cherr
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001559:Benzhydryl Compounds; D002140:California; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D045166:Estradiol Congeners / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000077267:Fulvestrant; D010140:Pacific Ocean; D010636:Phenols / Q000633:toxicity*; D012617:Sea Urchins / Q000187:drug effects* / Q000196:embryology; D013629:Tamoxifen / Q000494:pharmacology; D018675:Toxicity Tests; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004958:Estradiol; D045166:Estradiol Congeners; D000077267:Fulvestrant; D010636:Phenols; D013629:Tamoxifen; C080417:4-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds