Phthalates are used as solvents and plasticizers in a wide variety of consumer products. Most people are exposed to phthalates as parent compounds through ingestion, inhalation, and dermal contact. However, these parent compounds are quickly metabolized to more active compounds in several tissues. Although studies indicate that phthalate metabolites reach the ovary, little is known about whether they are ovarian toxicants. Thus, this study tested the hypothesis that phthalate metabolites influence the expression of genes involved in sex steroid synthesis, cell cycle regulation, cell death, oxidative stress, and key receptors, as well as production of sex steroid hormones by mouse antral follicles. The selected metabolite mixture consisted of 36.7% monoethyl phthalate (MEP), 19.4% mono(2-ethylhexyl) phthalate (MEHP), 15.3% monobutyl phthalate (MBP), 10.2% monoisobutyl phthalate (MiBP), 10.2% monoisononyl phthalate (MiNP), and 8.2% monobenzyl phthalate (MBzP). Antral follicles from adult CD-1 mice were cultured for 96 h with vehicle control (DMSO) or metabolite mixture (0.065-325 μg/mL). Growth of follicles in culture was monitored every 24 h. Total RNA was isolated after 24 and 96 h and used for gene expression analysis. Media were collected and subjected to hormone analysis. Exposure to the phthalate mixture inhibited follicle growth, decreased expression of steroidogenic enzymes, and altered the levels of sex steroids relative to control. The mixture, primarily at the two highest doses, also altered expression of cell cycle regulators, apoptotic factors, oxidative stress genes, and some receptors. Collectively, these data suggest that mixtures of phthalate metabolites can directly impact follicle health.

中文翻译：

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邻苯二甲酸酯代谢物混合物对小鼠肛门卵泡生长和性类固醇合成的影响。

邻苯二甲酸酯在多种消费品中用作溶剂和增塑剂。大多数人通过摄入，吸入和皮肤接触而暴露于邻苯二甲酸盐作为母体化合物。但是，这些母体化合物在几种组织中迅速代谢为活性更高的化合物。尽管研究表明邻苯二甲酸酯代谢物可以到达卵巢，但对它们是否是卵巢有毒物质了解甚少。因此，本研究检验了以下假设：邻苯二甲酸酯代谢物影响性类固醇合成，细胞周期调控，细胞死亡，氧化应激和关键受体，以及小鼠肛门卵泡中性类固醇激素的产生所涉及的基因的表达。选择的代谢物混合物包括36.7％的邻苯二甲酸单乙酯（MEP），19.4％的邻苯二甲酸单（2-乙基己基）酯（MEHP），15.3％的邻苯二甲酸单丁酯（MBP），10.2％的邻苯二甲酸单异丁酯（MiBP），10.2％的邻苯二甲酸单异壬酯（MiNP）和8.2％的邻苯二甲酸单苄酯（MBzP）。将成年CD-1小鼠的窦卵泡与媒介物对照（DMSO）或代谢产物混合物（0.065-325μg/ mL）培养96小时。每24小时监测培养物中卵泡的生长。在24和96小时后分离总RNA，并将其用于基因表达分析。收集培养基并进行激素分析。暴露于邻苯二甲酸盐混合物可抑制卵泡生长，降低类固醇生成酶的表达，并相对于对照改变性类固醇的水平。主要在两种最高剂量下的混合物也改变了细胞周期调节剂，凋亡因子，氧化应激基因和某些受体的表达。总的来说，