BACKGROUND Bisphenol A (BPA) is an endocrine disrupting chemical released from plastic materials, including food packaging and dental sealants, persisting in the environment and ubiquitously contaminating ecosystems and human populations. BPA can elicit an array of damaging health effects and, alarmingly, ‘BPA-free’ alternatives mirror these harmful effects. Bisphenol exposure can negatively impact female fertility, damaging both the ovary and oocytes therein. Such damage can diminish reproductive capacity, pregnancy success, and offspring health. Despite global government regulations in place to indicate ‘safe’ BPA exposure levels, these policies have not considered the effects of bisphenols on oocyte health. OBJECTIVE AND RATIONALE This scoping review was conducted to evaluate evidence on the effects of BPA and BPA alternatives on standardized parameters of oocyte health. In doing so, this review addresses a critical gap in the literature providing a comprehensive, up-to-date synthesis of the effects of bisphenols on oocyte health. SEARCH METHODS This scoping review was conducted in accordance with PRISMA guidelines. Four databases, Medline, Embase, Scopus, and Web of Science, were searched twice (23 February 2022 and 1 August 2023) to capture studies assessing mammalian oocyte health post-bisphenol exposure. Search terms regarding oocytes, ovarian follicles, and bisphenols were utilized to identify relevant studies. Manuscripts written in English and reporting the effect of any bisphenol on mammalian oocyte health from all years were included. Parameters for toxicological studies were evaluated, including the number of bisphenol concentrations/doses tested, dosing regimen, biological replicates and/or animal numbers, and statistical information (for human studies). Standardized parameters of oocyte health including follicle counts, oocyte yield, oocyte meiotic capacity, morphology of oocyte and cumulus cells, and oocyte meiotic spindle integrity were extracted across the studies. OUTCOMES After screening 3147 studies, 107 studies of either humans or mammalian animal models or humans were included. Of the in vitro exposure studies, 96.3% (26/27) and 94.1% (16/17) found at least one adverse effect on oocyte health using BPA or BPA alternatives (including BHPF, BPAF, BPB, BPF, and BPS), respectively. These included increased meiotic cell cycle arrest, altered morphology, and abnormal meiotic spindle/chromosomal alignment. In vivo, 85.7% (30/35) of studies on BPA and 92.3% (12/13) on BPA alternatives documented adverse effects on follicle development, morphology, or spindle/chromosome alignment. Importantly, these effects were recorded using levels below those deemed ‘safe’ for human exposure. Over half (11/21) of all human observational studies showed associations between higher urinary BPA levels and reduced antral follicle counts or oocyte yield in IVF patients. Recommendations are presented based on the identified shortcomings of the current evidence, incorporating elements of FDA requirements for future research in the field. WIDER IMPLICATIONS These data highlight the detrimental impacts of low-level BPA and BPA alternative exposure, contributing to poor oocyte quality and reduced fertility. These outcomes are valuable in promoting the revision of current policies and guidelines pertaining to BPA exposure internationally. This study serves as a valuable resource to scientists, providing key recommendations on study design, reporting elements, and endpoint measures to strengthen future studies. Ultimately, this review highlights oocyte health as a fundamentally important endpoint in reproductive toxicological studies, indicating an important direction for future research into endocrine disrupting chemicals to improve fertility outcomes.

中文翻译：

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双酚 A 及其替代品对卵母细胞健康的影响：范围综述


背景 双酚 A （BPA） 是一种从塑料材料（包括食品包装和牙科密封剂）中释放的内分泌干扰化学物质，持续存在于环境中并无处不在地污染生态系统和人类。BPA 会引发一系列破坏性的健康影响，令人担忧的是，“不含 BPA”的替代品反映了这些有害影响。双酚暴露会对女性的生育能力产生负面影响，损害卵巢和其中的卵母细胞。这种损害会降低生殖能力、怀孕成功率和后代健康。尽管全球政府出台了相关法规来表明“安全”的 BPA 暴露水平，但这些政策并未考虑双酚对卵母细胞健康的影响。客观和基本原理 进行本范围审查是为了评估 BPA 和 BPA 替代品对卵母细胞健康标准化参数影响的证据。在此过程中，本综述解决了文献中的一个关键空白，提供了双酚对卵母细胞健康影响的全面、最新的综合。检索方法 本范围综述是根据 PRISMA 指南进行的。检索了 Medline、Embase、Scopus 和 Web of Science 四个数据库两次（2022 年 2 月 23 日和 2023 年 8 月 1 日），以捕获评估双酚暴露后哺乳动物卵母细胞健康状况的研究。使用有关卵母细胞、卵巢卵泡和双酚的检索词来确定相关研究。包括用英文撰写的手稿，并报告了所有年份任何双酚对哺乳动物卵母细胞健康的影响。评估了毒理学研究的参数，包括测试的双酚浓度/剂量的数量、给药方案、生物学重复和/或动物数量以及统计信息（用于人类研究）。 在研究中提取了卵母细胞健康的标准化参数，包括卵泡计数、卵母细胞产量、卵母细胞减数分裂能力、卵母细胞和卵丘细胞的形态以及卵母细胞减数分裂纺锤体完整性。结果 筛选 3147 项研究后，纳入了 107 项人类或哺乳动物模型或人类的研究。在体外暴露研究中，96.3% （26/27） 和 94.1% （16/17） 发现使用 BPA 或 BPA 替代品（包括 BHPF、BPAF、BPB、BPF 和 BPS）分别对卵母细胞健康至少有一种不利影响。这些包括减数分裂细胞周期停滞增加、形态改变和减数分裂纺锤体/染色体排列异常。在体内，85.7% （30/35） 的 BPA 研究和 92.3% （12/13） 的 BPA 替代品研究记录了对卵泡发育、形态或纺锤体/染色体排列的不利影响。重要的是，这些影响是使用低于被认为对人类暴露“安全”的水平来记录的。超过一半 （11/21） 的人类观察研究表明，IVF 患者较高的尿 BPA 水平与胃窦卵泡计数或卵母细胞产量降低之间存在关联。根据当前证据的已确定缺陷提出建议，并纳入了 FDA 对该领域未来研究的要求要素。更广泛的影响 这些数据强调了低水平 BPA 和 BPA 替代暴露的有害影响，导致卵母细胞质量差和生育能力下降。这些结果对于促进国际上与 BPA 暴露相关的当前政策和指南的修订很有价值。这项研究为科学家提供了宝贵的资源，为研究设计、报告要素和终点措施提供了关键建议，以加强未来的研究。 最终，本综述强调卵母细胞健康是生殖毒理学研究中一个根本重要的终点，为未来研究内分泌干扰化学物质以改善生育结果指明了重要方向。