Steroidogenesis-disrupting compounds can be effectively studied for major fertility-related endpoints using in vitro cultured mouse follicles
Steroidogenesis-disrupting compounds can be effectively studied for major fertility-related endpoints using in vitro cultured mouse follicles
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DOI：
10.1016/j.toxlet.2008.12.015
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发表时间：
2009-03-28
影响因子：
3.5
通讯作者：
Smitz, Johan
中科院分区：
文献类型：
--
作者：
Lenie, Sandy;Smitz, Johan
需要进行生物学相关的生物测定来测试各种内分泌干扰物（ED）。小鼠卵泡培养模型可以使用常规方法测量类固醇生成酶的功能以及卵母细胞生长和减数分裂成熟。测试了三种破坏类固醇生成的“模型”化学物质；伏罗唑 (VOR)、氨基鲁米特 (AMG) 和酮康唑 (KCZ)。除了通过传统光学显微镜对卵泡生长、分化以及卵母细胞生长和成熟进行视觉评估外，类固醇分泌测量还可以证实来自体内动物研究和更复杂的体外测试的文献发现。该生物测定法用于邻苯二甲酸单(2-乙基己基)酯 (MEHP) 的剂量反应研究，MEHP 是一种已知会破坏多种类固醇生成酶的化学物质。该生物测定能够证实 E-2 对 E-1 的失活增加以及诱导的早熟孕酮增加，这意味着 MEHP 可以破坏卵泡分化并影响生殖轴。这种体外卵巢模型可以通过对大量早期腔前卵巢小鼠卵泡进行同步培养来减少动物的使用，并且可以提供多种生育相关终点的信息。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
Biologically relevant bioassays are needed to test various endocrine disrupters (EDs). A mouse follicle culture model could allow measuring steroidogenic enzyme function in combination with oocyte growth and meiotic maturation using routine methodology. Three steroidogenesis-disrupting 'model' chemicals were tested; vorozole (VOR), aminoglutethimide (AMG), and ketoconazole (KCZ). Along with visual assessment of follicular growth, differentiation and oocyte growth and maturation by conventional light microscopy, steroid secretion measurements allowed to confirm literature findings from in vivo animal studies and more complex in vitro tests. The bioassay was applied for a dose-response study of mono(2-ethyl hexyl)phthalate (MEHP), a chemical known to disrupt several steroidogenic enzymes. This bioassay was able to confirm an increased inactivation of E-2 to E-1 and an induced precocious progesterone increase, implying that MEHP can disrupt follicle differentiation and impact the reproductive axis. This in vitro ovarian model allows to reduce animal use by performing synchronous culture of large numbers of early preantral ovarian mouse follicles and is informative on multiple fertility-related endpoints. (C) 2008 Elsevier Ireland Ltd. All rights reserved.