Disruption of sensitive stages of ovary development during fetal and perinatal life can have severe and life-long consequences for a woman's reproductive life. Exposure to endocrine disrupting chemicals may affect ovarian development, leading to subsequent reproductive disorders. Here, we investigated the effect of early life exposure to defined mixtures of human-relevant endocrine disrupting chemicals on the rat ovary. We aimed to identify molecular events involved in pathogenesis of ovarian dysgenesis syndrome that have potential for future adverse outcome pathway development. We therefore focused on the ovarian proteome. Rats were exposed to a mixture of phthalates, pesticides, UV-filters, bisphenol A, butyl-paraben, and paracetamol during gestation and lactation. The chemicals were tested together or in subgroups of chemicals with anti-androgenic or estrogenic potentials at doses 450-times human exposure. Paracetamol was tested separately, at a dose of 360 mg/kg. Using shotgun proteomics on ovaries from pup day 17 offspring, we observed exposure effects on the proteomes. Nine proteins were affected in more than one exposure group and of these, we conclude that calretinin is a potential key event biomarker of early endocrine disruption in the ovary.

中文翻译：

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Calretinin 是一种新的候选标记物，用于早期暴露于大鼠内分泌干扰物混合物对卵巢的不良影响。

胎儿和围产期卵巢发育敏感阶段的中断可能对女性的生殖生活产生严重和终生的影响。接触内分泌干扰化学物质可能会影响卵巢发育，导致随后的生殖障碍。在这里，我们调查了早期暴露于特定的与人类相关的内分泌干扰化学物质混合物对大鼠卵巢的影响。我们旨在确定与卵巢发育不全综合征发病机制相关的分子事件，这些事件具有未来不良结果通路发展的潜力。因此，我们专注于卵巢蛋白质组。大鼠在妊娠和哺乳期间暴露于邻苯二甲酸盐、杀虫剂、紫外线过滤剂、双酚 A、对羟基苯甲酸丁酯和扑热息痛的混合物中。这些化学物质一起或在具有抗雄激素或雌激素潜力的化学物质亚组中进行了测试，剂量是人体暴露量的 450 倍。对乙酰氨基酚单独测试，剂量为 360 mg/kg。对第 17 天幼犬后代的卵巢使用猎枪蛋白质组学，我们观察到暴露对蛋白质组的影响。九种蛋白质在不止一个暴露组中受到影响，其中我们得出结论，钙调蛋白是卵巢早期内分泌紊乱的潜在关键事件生物标志物。