Use of an organotypic mammalian in vitro follicle growth assay to facilitate female reproductive toxicity screening.
Use of an organotypic mammalian in vitro follicle growth assay to facilitate female reproductive toxicity screening.
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使用器官型哺乳动物体外卵泡生长测定来促进雌性生殖毒性筛查。
DOI：
10.1071/rd14375
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Woodruff,TeresaK
中科院分区：
文献类型：
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作者：
Xu,Yuanming;Duncan,FrancescaE;Xu,Min;Woodruff,TeresaK
筛选药物、化学和环境化合物对生殖健康的影响依赖于体内研究。需要更稳健和有效的方法来评估这些影响。在此，我们采用并验证了器官型体外卵泡生长（IVFG）测定，以确定化合物对卵巢功能标志物的影响。我们分离了哺乳动物卵泡，并在存在以下化合物的情况下培养它们：（1）已知的生育毒性（即对生殖系统的毒性；环磷酰胺和顺铂）； (2) 没有已知的生育毒性（纳布啡）； (3) 未知的生育毒性（Corexit EC 9500 A；CE，Nalco，芝加哥，伊利诺伊州，美国）。对于每种化合物，我们检测了卵泡生长、激素产生以及卵泡封闭卵母细胞恢复减数分裂和产生成熟卵子的能力。环磷酰胺和顺铂会造成卵泡动力学的剂量依赖性破坏，而纳布啡则不会。 CE 是一种在 2010 年深水地平线漏油事件中大量使用的石油分散剂，其生殖毒性从未在哺乳动物系统中进行过研究。在本研究中，CE 损害了卵泡形态和功能参数。我们的研究结果表明，这种 IVFG 检测系统可用于区分生育毒性化合物和无毒化合物，为评估化合物对生殖功能和健康的影响提供了体外工具。
Screening of pharmaceutical, chemical and environmental compounds for their effects on reproductive health relies on in vivo studies. More robust and efficient methods to assess these effects are needed. Herein we adapted and validated an organotypic in vitro follicle growth (IVFG) assay to determine the impact of compounds on markers of ovarian function. We isolated mammalian follicles and cultured them in the presence of compounds with: (1) known fertotoxicity (i.e. toxicity to the reproductive system; cyclophosphamide and cisplatin); (2) no known fertotoxicity (nalbuphine); and (3) unknown fertotoxicity (Corexit EC 9500 A; CE, Nalco, Chicago, IL, USA). For each compound, we assayed follicle growth, hormone production and the ability of follicle-enclosed oocytes to resume meiosis and produce a mature egg. Cyclophosphamide and cisplatin caused dose-dependent disruption of follicle dynamics, whereas nalbuphine did not. The reproductive toxicity of CE, an oil dispersant used heavily during the 2010 Deepwater Horizon oil spill, has never been examined in a mammalian system. In the present study, CE compromised follicle morphology and functional parameters. Our findings demonstrate that this IVFG assay system can be used to distinguish fertotoxic from non-toxic compounds, providing an in vitro tool to assess the effects of chemical compounds on reproductive function and health.