Jessl Luzie, Lenz Rebecca, Massing Fabian G, Scheider Jessica, Oehlmann Jörg
Department Aquatic Ecotoxicology, Johann Wolfgang Goethe Universität Frankfurt am Main, Frankfurt am Main, Hesse, Germany.
R-Biopharm AG, Darmstadt, Hesse, Germany.
PeerJ. 2018 Jul 3;6:e5094. doi: 10.7717/peerj.5094. eCollection 2018.
Since it is known that environmental contaminants have the potential to cause endocrine disorders in humans and animals, there is an urgent need for in vivo tests to assess possible effects of these endocrine disrupting chemicals (EDCs). Although there is no standardized guideline, the avian embryo has proven to be particularly promising as it responds sensitively to a number of EDCs preferentially impacting the reproductive axis. In the present study we examined the effects of in ovo exposure to fulvestrant and tamoxifen as antiestrogenic model compounds and co-exposure to both substances and the potent estrogen 17α-ethinylestradiol (EE) regarding sex differentiation and embryonic development of the domestic fowl (). The substances were injected into the yolk of fertilized eggs on embryonic day 1. On embryonic day 19 sex genotype and phenotype were determined, followed by gross morphological and histological examination of the gonads. Sole EE-treatment (20 ng/g egg) particularly affected male gonads and resulted in an increased formation of female-like gonadal cortex tissue and a reduction of seminiferous tubules. In ovo exposure to tamoxifen (0.1/1/10 µg/g egg) strongly impaired the differentiation of female gonads, led to a significant size reduction of the left ovary and induced malformations of the ovarian cortex, while fulvestrant (0.1/1/10 µg/g egg) did not affect sexual differentiation. However, both antiestrogens were able to antagonize the feminizing effects of EEin genetic males when administered simultaneously. Since both estrogens and antiestrogens induce concentration-dependent morphological alterations of the sex organs, the chick embryo can be regarded as a promising model for the identification of chemicals with estrogenic and antiestrogenic activity.
由于已知环境污染物有可能导致人类和动物的内分泌紊乱,因此迫切需要进行体内试验,以评估这些内分泌干扰化学物质(EDC)可能产生的影响。尽管没有标准化的指南,但事实证明,禽类胚胎特别有前景,因为它对优先影响生殖轴的多种EDC反应敏感。在本研究中,我们研究了在鸡蛋内暴露于氟维司群和他莫昔芬这两种抗雌激素模型化合物,以及同时暴露于这两种物质和强效雌激素17α-乙炔雌二醇(EE)对家鸡性别分化和胚胎发育的影响。在胚胎第1天,将这些物质注射到受精卵的卵黄中。在胚胎第19天确定性别基因型和表型,随后对性腺进行大体形态学和组织学检查。单独使用EE处理(20 ng/g鸡蛋)对雄性性腺影响尤为明显,导致类似雌性的性腺皮质组织形成增加,生精小管减少。在鸡蛋内暴露于他莫昔芬(0.1/1/10 µg/g鸡蛋)会严重损害雌性性腺的分化,导致左卵巢显著变小,并诱导卵巢皮质畸形,而氟维司群(0.1/1/10 µg/g鸡蛋)不影响性别分化。然而,当同时给药时,这两种抗雌激素都能够拮抗EE对遗传雄性的雌性化作用。由于雌激素和抗雌激素都会诱导性器官出现浓度依赖性的形态改变,因此鸡胚胎可被视为一种有前景的模型,用于鉴定具有雌激素和抗雌激素活性的化学物质。