Berni M, Gigante P, Bussolati S, Grasselli F, Grolli S, Ramoni R, Basini G
Dipartimento di Scienze Medico-Veterinarie, Università di Parma, Via del Taglio 10, Parma 43126, Italy.
Dipartimento di Scienze Medico-Veterinarie, Università di Parma, Via del Taglio 10, Parma 43126, Italy.
Domest Anim Endocrinol. 2019 Jan;66:48-56. doi: 10.1016/j.domaniend.2018.08.001. Epub 2018 Aug 23.
The high-volume-produced plastic monomer Bisphenol A (BPA) has been in the spotlight in the last years because of its endocrine disruptor (ED) behavior, leading to disclosure of the association between the widespread human and wildlife exposure to BPA and reproductive, metabolic, and developmental disorders and hormone-dependent cancer onset. These evidences caused restrictions and prohibitions of BPA industrial uses and prompted investigation of harmless alternative compounds. Above all, several countries have substituted the parental analogue with Bisphenol S (BPS) in baby care product manufacturing, even if its structural homology to BPA suggests similar ED properties not yet completely ruled out. In light of this consideration, the aim of this in vitro study was to investigate the effect of BPS exposure (0.1, 1, and 10 μM for 48 h) on granulosa cells that are considered the prime ovarian targets of BPA as a "reproductive toxicant". Our data document that BPS inhibited E2 production, cell proliferation, and scavenging nonenzymatic activity (P < 0.05) while it significantly (P < 0.05) stimulated cell viability, superoxide (O) and nitric oxide (NO) production in cultured swine granulosa cells, a previously validated endocrine cell model for BPA. Evidence also exists that BPA and its analogues, as environmental lipophilic pollutants, are involved in the disruption of adipose tissue (AT) endocrine function, resulting in metabolic effects and thus in potential reproductive disorders. On this basis, our second purpose was the assessment of BPS effects on mesenchymal stromal cells (MSCs) isolated from porcine AT, taking into account MSCs viability and adipogenic differentiation, a process actually demonstrated to be largely affected by EDs. Our results show that BPS decreased (P < 0.001) cell viability of proliferating adipose stromal cells. Taken as a whole, our data demonstrate an effective BPS ED activity at μM concentrations, suggesting that further studies are needed before considering its use in industrial application as an alternative to BPA.
高产量生产的塑料单体双酚A（BPA）在过去几年中备受关注，因为其具有内分泌干扰物（ED）的特性，这使得广泛存在于人类和野生动物体内的BPA暴露与生殖、代谢、发育障碍以及激素依赖性癌症发病之间的关联得以揭示。这些证据导致了对BPA工业用途的限制和禁令，并促使人们对无害替代化合物进行研究。最重要的是，几个国家在婴儿护理产品制造中用双酚S（BPS）替代了母体类似物，尽管BPS与BPA的结构同源性表明其类似的ED特性尚未完全排除。鉴于此，本体外研究的目的是调查BPS暴露（分别为0.1、1和10 μM，持续48小时）对颗粒细胞的影响，颗粒细胞被认为是BPA作为“生殖毒物”的主要卵巢靶标。我们的数据表明，BPS抑制了E2的产生、细胞增殖和非酶清除活性（P < 0.05），而在培养的猪颗粒细胞（一种先前已验证的BPA内分泌细胞模型）中，它显著（P < 0.05）刺激了细胞活力、超氧化物（O）和一氧化氮（NO）的产生。也有证据表明，BPA及其类似物作为环境亲脂性污染物，参与了脂肪组织（AT）内分泌功能的破坏，导致代谢效应，进而引发潜在的生殖障碍。在此基础上，我们的第二个目的是评估BPS对从猪AT分离的间充质基质细胞（MSCs）的影响，同时考虑MSCs的活力和成脂分化，这一过程实际上已被证明在很大程度上受EDs影响。我们的结果表明，BPS降低了增殖期脂肪基质细胞的细胞活力（P < 0.001）。总体而言，我们的数据证明了BPS在μM浓度下具有有效的ED活性，这表明在考虑将其作为BPA的替代品用于工业应用之前，还需要进一步研究。
