Early estrogen exposure induces abnormal development of Fundulus heteroclitus

Abstract

Many chemicals released into the environment exhibit estrogenic activity, having the potential to disrupt development and the functioning of the endocrine system. In order to establish a model system to study the effects of such environmental chemicals on aquatic animals, we examined the effects of a natural estrogen, 17 beta-estradiol (E(2)), on early development of Fundulus heteroclitus. Embryos of F. heteroclitus were reared in seawater containing 10(-10), 10(-8), and 10(-6) M E(2) throughout the experiment. Hatching and survival rates decreased in a dose-dependent manner, and fry treated with 10(-6) M E(2) and 10(-8) M E(2) were dead by two weeks and 12 weeks after hatching, respectively. More than 85% of fry treated with 10(-8) M E(2) showed malformations: i.e., eye extrusion, crooked vertebral column, faded lateral-stripe pattern eight weeks after hatching. Body weight and head and body lengths were significantly reduced in E(2)-treated fry when compared to controls. Ossification was not completed in vertebrae, cranial bones, and other bones in fry treated with 10(-8) M E(2) even 12 weeks after hatching. Sex ratio of control fry was 57% male and 43% female, whereas fry treated with 10(-8) M E(2) were 100% female eight weeks after hatching. The present results demonstrate that exogenous estrogen induced death of embryos and fry, malformations, sex reversal, and incomplete ossification of vertebrae and cranial bones, which would result in shorter body and head lengths and in malformed vertebrae leading to a hunchback condition.

Exposures to Estradiol, Ethinylestradiol and Octylphenol Affect Survival and Growth ofRana pipiens and Rana sylvaticaTadpoles

“…In Nishimura et al (1997), exposure to 1 μM E 2 accelerated the rate of development in Xenopus laevis tadpoles; both body weight and mean developmental stage were higher in the E 2 -treated group relative to the control group. Contrary results were seen after E 2 exposure (0.1 nM, 10 nM E 2 ) of mummichog (Fundulus heteroclitus) fry, where body weights were significantly reduced compared to control (Urushitani et al, 2002). In both studies, growth effects were observed after a prolonged exposure to the hormone.…”

Estradiol uptake, toxicity, metabolism, and adverse effects on cadmium-treated amphibian embryos.

“…For example, in Xenopus laevis embryos, different natural and synthetic estrogens induce malformations of the head and abdomen, suppress organogenesis, and exert lethality (Nishimura et al 1997). In Fundulus heteroclitus, 0.01 and 1 µmol/L E 2 in the maintaining medium induces death of embryos and fry, malformations, sex reversal, and incomplete ossification of vertebrae and cranial bones, which would result in shorter body and head lengths and in malformed vertebrae, leading to a hunchback condition (Urushitani et al 2002). Kishida et al (2001) reported that the treatment of zebrafish embryos (Danio rerio) with 0.1-10 µmol/L E 2 between 2 and 72 hr postfertilization provoked dose-response effects on mortality and hatching and induced the "curved tail down" phenotype characteristically similar to mutants with defects in the central nervous system.…”

Effects of 17α-ethynylestradiol on early-life development, sex differentiation and vitellogenin induction in mummichog (Fundulus heteroclitus)

“…Sheepshead minnow exposed to EE 2 showed reduced egg production at 20 and 200 ng/L and reduced hatching at 200 ng/ L (Zillioux et al, 2001). Hatching success decreased in a dosedependent manner in larval mummichog exposed to estradiol (E 2 ) (Urushitani et al, 2002) and estrogenic alkylphenols caused complete larval mortality at concentrations P10 lM and hatching success was <10% below this concentration (Kelly and Di Giulio, 2000).…”

“…The fathead minnow has a period of enhanced sensitivity to EE 2 between 10 and 15 days post-hatch, when male fish are more likely to develop female characteristics (Van Aerle et al, 2002) and 6-day exposures with medaka have demonstrated that exposure while an embryo, newly hatched fry or 1 week post-hatch are sufficient to alter sex ratios and/or develop intersex gonads at sexual maturity (Koger et al, 2000). In mummichog, the window of sensitivity to exogenous steroids during differentiation has not been precisely identified but most likely occurs from 2-4 weeks after hatching (Urushitani et al, 2002). EE 2 is typically found in low concentrations (0.1-10 ng/L with amounts as high as 42 ng/L in some cases) in Canadian sewage effluents (Desbrow et al, 1998;Ternes et al, 1999).…”