Gyllenhammar Irina, Holm Lena, Eklund Rosita, Berg Cecilia
Department of Environmental Toxicology, Uppsala University, Centre for Reproductive Biology in Uppsala (CRU), Norbyvägen 18A, 75236 Uppsala, Sweden.
Aquat Toxicol. 2009 Jan 31;91(2):171-8. doi: 10.1016/j.aquatox.2008.06.019. Epub 2008 Jul 15.
Reproductive disorders in wildlife and humans have been linked to developmental exposure to endocrine disrupting chemicals. In frog tadpoles, environmental concentrations of ethynylestradiol (EE(2)) disrupt gonadal differentiation which results in female-biased sex ratios at metamorphosis indicating sex-reversal of genotypic males. It is not known if developmental exposure to estrogens results in reduced reproductive success in amphibians. The objective of this work was to investigate if exposure to environmentally relevant concentrations of EE(2) during sex differentiation impairs reproductive organ development, fertility, and sexual behavior in adult frogs. A specific aim was to evaluate if testicular structure and function was affected in males that were not sex-reversed. Xenopus tropicalis tadpoles were exposed until metamorphosis to 6, 60, and 600 pM EE(2). Eight months after metamorphosis, reproductive organ morphology and fertility were evaluated. Larval EE(2)-exposure caused an increased proportion of phenotypic females indicating that sex-reversal of genotypic males is persistent. Sex-reversal was implied at concentrations as low as 6 pM (1.8 ng/l), which is comparable to levels observed in the environment. EE(2)-exposed males that were not sex-reversed had a significantly reduced fertilization rate compared with control males. Histological evaluation revealed that EE(2)-exposed males had a reduced amount of spermatozoa in the testis. Among frogs with ovaries there was a significantly higher percentage that lacked oviducts in the group exposed to 600 pM EE(2) compared with control females. No effect of EE(2) on sexual behavior was noted. The results indicate that reproduction in wild frogs might be impaired by estrogenic environmental pollutants. Similarities between the present effects and those reported in fish, birds and mammals after developmental exposure to estrogens suggest that X. tropicalis is a promising animal model for research on developmental reproductive toxicity.
野生动物和人类的生殖障碍与发育过程中接触内分泌干扰化学物质有关。在蛙蝌蚪中，环境浓度的乙炔雌二醇（EE(2)）会扰乱性腺分化，导致变态时雌性偏向的性别比例，表明基因型雄性发生了性逆转。目前尚不清楚发育过程中接触雌激素是否会导致两栖动物的繁殖成功率降低。这项工作的目的是研究在性别分化期间接触环境相关浓度的EE(2)是否会损害成年青蛙的生殖器官发育、生育能力和性行为。一个具体目标是评估未发生性逆转的雄性青蛙的睾丸结构和功能是否受到影响。热带爪蟾蝌蚪在变态前暴露于6、60和600 pM的EE(2)中。变态后八个月，评估生殖器官形态和生育能力。幼虫期暴露于EE(2)导致表型雌性的比例增加，表明基因型雄性的性逆转是持续的。在低至6 pM（1.8 ng/l）的浓度下就暗示了性逆转，这与环境中观察到的水平相当。与对照雄性相比，未发生性逆转的EE(2)暴露雄性的受精率显著降低。组织学评估显示，EE(2)暴露雄性的睾丸中精子数量减少。在有卵巢的青蛙中，与对照雌性相比，暴露于600 pM EE(2)的组中缺乏输卵管的百分比显著更高。未观察到EE(2)对性行为有影响。结果表明，野生青蛙的繁殖可能会受到雌激素性环境污染物的损害。目前的影响与发育过程中接触雌激素后在鱼类、鸟类和哺乳动物中报道的影响之间的相似性表明，热带爪蟾是研究发育性生殖毒性的一个有前途的动物模型。
