INRAE, CNRS, Université de Tours, PRC, Nouzilly, 37380, France.
INRAE, PAO, Nouzilly, 37380, France.
BMC Genomics. 2024 Nov 16;25(1):1095. doi: 10.1186/s12864-024-11034-2.
Bisphenol S (BPS) is the main substitute for bisphenol A (BPA), a well-known plasticiser and endocrine disruptor. BPS disrupts ovarian function in several species. Moreover, a few studies have reported that the effects of BPS might be modulated by the metabolic status, and none have characterised the granulosa cell (GC) proteome after chronic BPS exposure.
This study aimed to decipher the mechanisms of action of chronic BPS exposure on the proteome of ewe GCs while considering the interaction between a deliberate contrasted metabolism and reproductive function.
Forty ewes were split into two groups with contrasted diets: restricted (R, n = 20) and well-fed (WF, n = 20). The R and WF ewes were subdivided according to the dose of BPS administered through the diet (0-50 µg/kg/day), forming four groups: R0, R50, WF0 and WF50. After 3-month BPS daily exposure, GCs were recovered during the pre-ovulatory stage and proteins were analysed by nano-liquid chromatography coupled with tandem mass spectrometry.
Chronic exposure to BPS affected the GC proteome differently according to the ewe metabolic status. Fifty-nine out of 958 quantified proteins were differentially abundant between groups and are mainly involved in carbohydrate and lipid pathways. Unsupervised hierarchical clustering of differentially abundant proteins (DAPs) identified four clusters of 34, 6, 5 and 14 proteins according to the BPS exposure and diet interaction. Pairwise comparisons between groups also revealed a strong effect of BPS exposure and diet interaction. Functional analysis of DAPs highlighted that BPS upregulated β-glucuronidase (GUSB; p = 0.002), a protein especially able to deconjugate bisphenol glucuronides (BP-g). Moreover, among unexposed ewes, GUSB was detected only in well-fed ewes.
Conjugation of glucuronides inhibits the oestrogenic activity of bisphenols. Upregulation of GUSB in ewes dosed with BPS would prolong the oestrogenic effects of BPS by deconjugating BPS-g into free BPS. In addition, literature has reported an up-regulation of GUSB in people suffering from obesity. Therefore, people suffering from obesity could be subjected to prolonged and aggravated exposure to BPS. These data highlighted the deleterious effects of BPS and its interaction with metabolic status.
双酚 S（BPS）是双酚 A（BPA）的主要替代品，BPA 是一种众所周知的增塑剂和内分泌干扰物。BPS 会破坏几种物种的卵巢功能。此外，一些研究报告称，BPS 的影响可能受到代谢状态的调节，但没有研究描述过慢性 BPS 暴露后颗粒细胞（GC）的蛋白质组。
本研究旨在阐明慢性 BPS 暴露对绵羊 GC 蛋白质组的作用机制，同时考虑到故意对比代谢和生殖功能之间的相互作用。
将 40 只绵羊分为两组，给予不同的饮食：限制（R，n=20）和充足（WF，n=20）。根据通过饮食给予的 BPS 剂量（0-50μg/kg/天），将 R 和 WF 绵羊分为两组：R0、R50、WF0 和 WF50。在 3 个月的 BPS 每日暴露后，在排卵前阶段回收 GC，并通过纳升液相色谱与串联质谱分析蛋白质。
根据绵羊的代谢状态，慢性 BPS 暴露对 GC 蛋白质组的影响不同。在组间有 958 种定量蛋白中，有 59 种蛋白的丰度有差异，这些蛋白主要参与碳水化合物和脂质代谢途径。根据 BPS 暴露和饮食相互作用，对差异丰度蛋白（DAP）进行无监督层次聚类，确定了 34、6、5 和 14 个蛋白的 4 个聚类。组间的两两比较也显示出 BPS 暴露和饮食相互作用的强烈影响。DAP 的功能分析突出表明，BPS 上调了β-葡糖苷酸酶（GUSB；p=0.002），这是一种特别能够使结合物脱共轭的蛋白质。此外，在未暴露的绵羊中，仅在充足饮食的绵羊中检测到 GUSB。
葡萄糖醛酸结合物抑制了双酚类物质的雌激素活性。在给予 BPS 的绵羊中 GUSB 的上调会通过将 BPS-g 脱共轭为游离 BPS 而延长 BPS 的雌激素作用。此外，文献报道肥胖患者的 GUSB 上调。因此，肥胖患者可能会长期且加重地暴露于 BPS 下。这些数据强调了 BPS 的有害影响及其与代谢状态的相互作用。
