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暴露于三种内分泌干扰物后,轮虫秀丽隐杆线虫中两种视黄酸信号通路受体的表达变化。

Expression variations of two retinoid signaling pathway receptors in the rotifer Brachionus calyciflorus exposed to three endocrine disruptors.

机构信息

Laboratory of Animal Ecology and Ecotoxicology (LEAE)-Freshwater and OceaniC sciences Unit of reSearch (FOCUS), Chemistry Institute, B ât. B6C, University of Liège, 11 allée du 6 Août, Sart-Tilman, B-4000, Liège, Belgium.

出版信息

Ecotoxicology. 2021 Mar;30(2):343-350. doi: 10.1007/s10646-020-02339-5. Epub 2021 Jan 14.

DOI:10.1007/s10646-020-02339-5
PMID:33443716
Abstract

Endocrine disruption compounds (EDC) are known to affect reproduction, development, and growth of exposed organisms. Although in vertebrates, EDCs mainly act through steroid receptors (e.g. androgen and estrogen receptors), their absence in many invertebrates suggests the involvement of another biological pathway in endocrine disruption effects. As retinoid signaling pathway is present in almost all Metazoa and its involvement in the endocrine disruption of gastropods (i.e. imposex) has been demonstrated, the present work was devoted to investigating the relative mRNA variations of two retinoid receptors genes, retinoid X receptor (RXR) and retinoid acid receptor (RAR), in the freshwater rotifer Brachionus calyciflorus exposed for 6, 12 and 24 h to flutamide, fenitrothion and cyproterone acetate, three anti-androgens known to disrupt sexual reproduction of Brachionus sp. Results revealed that fenitrothion did not affect the relative mRNA levels RXR and RAR in B. calyciflorus, whereas RXR and RAR mRNA levels could be significantly increased by 2 to 4.5-fold and from 2 to 7-fold after exposure to flutamide and cyproterone acetate, respectively. Moreover, the effects of flutamide and cyproterone acetate were measured from 6 and 12 h of exposure, respectively. Cyproterone acetate caused the highest increase of RXR and RAR mRNA levels, probably due to its progestin activity in addition to its anti-androgenic activity and the potential presence of a membrane-associated progesterone receptor as reported in Brachionus manjavacas. Consequently, although it is still difficult to evaluate the hormonal pathways involved in the endocrine disruption in Brachionus sp., this work suggests that the retinoid signaling pathway appears to be a good starting point to try to elucidate the molecular mechanisms involved in sexual reproductive dysfunction in Brachionidae.

摘要

内分泌干扰化合物(EDC)已知会影响暴露生物的生殖、发育和生长。尽管在脊椎动物中,EDC 主要通过类固醇受体(如雄激素和雌激素受体)发挥作用,但许多无脊椎动物缺乏这些受体表明,内分泌干扰效应可能涉及另一种生物途径。由于视黄酸信号通路几乎存在于所有后生动物中,并且其在内脏门(即雌雄同体)内分泌干扰中的作用已得到证实,因此本工作致力于研究两种视黄酸受体基因(RXR 和 RAR)的相对 mRNA 变化在淡水轮虫 Brachionus calyciflorus 中,轮虫暴露于氟他胺、fenitrothion 和 cyproterone acetate 中 6、12 和 24 小时,这三种抗雄激素已知会破坏 Brachionus sp. 的生殖繁殖。结果表明,fenitrothion 不会影响 B. calyciflorus 中 RXR 和 RAR 的相对 mRNA 水平,而 RXR 和 RAR mRNA 水平分别在暴露于氟他胺和 cyproterone acetate 2 至 4.5 倍和 2 至 7 倍后显著增加。此外,氟他胺和 cyproterone acetate 的作用分别在暴露 6 和 12 小时后测量。cyproterone acetate 导致 RXR 和 RAR mRNA 水平的增加最高,可能是由于其孕激素活性,除了其抗雄激素活性和在 Brachionus manjavacas 中报道的潜在存在膜相关孕激素受体。因此,尽管仍然难以评估 Brachionus sp. 中内分泌干扰涉及的激素途径,但这项工作表明视黄酸信号通路似乎是阐明 Brachionidae 生殖功能障碍涉及的分子机制的一个很好的起点。

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