Herrera-Cogco Elena, López-Bayghen Bruno, Hernández-Melchor Dinorah, López-Luna Almena, Palafox-Gómez Cecilia, Ramírez-Martínez Leticia, López-Bello Estheisy, Albores Arnulfo, López-Bayghen Esther
Departamento de Toxicología, Centro de Investigación de Estudios Avanzados del IPN, México City, México.
Laboratorio de Investigación y Diagnóstico Molecular, Instituto de Infertilidad y Genética, México City, México.
Toxicol Mech Methods. 2020 Jun;30(5):336-349. doi: 10.1080/15376516.2020.1741052. Epub 2020 Mar 29.
In cosmetics and food products, parabens are widely used as antimicrobial agents. Reports have suggested that parabens may be linked to infertility, owing to their effects on basal steroidogenesis properties or their capacity to inflict mitochondrial damage. Despite growing concerns about parabens as endocrine disruptors, it is unclear whether they affect any of these actions in humans, particularly at environmentally relevant concentrations. In this work, an primary culture of human granulosa cells was used to evaluate steroidogenesis, based on the assessment of progesterone production and regulation of critical steroidogenic genes: , , , and . The effects of two commercially relevant parabens, methylparaben (MPB) and butylparaben (BPB), were screened. Cells were exposed to multiple concentrations ranging from relatively low (typical environmental exposure) to relatively high. The effect was assessed by the parabens' ability to modify steroidogenic genes, progesterone or estradiol production, and on mitochondrial health, by evaluating mitochondrial activity as well as mtDNA content. Neither MPB nor BPB showed any effect over progesterone production or the expression of genes controlling steroid production. Only BPB affected the mitochondria, decreasing mtDNA content at supraphysiological concentrations (1000 nM). Prolonged exposure to these compounds produced no effects in neither of these parameters. In conclusion, neither MPB nor BPB significantly affected basal steroidogenesis in granulosa cells. Although evidence supporting paraben toxicity is prevalent, here we put forth evidence that suggests that parabens do not affect basal steroidogenesis in human granulosa cells.
在化妆品和食品中,对羟基苯甲酸酯被广泛用作抗菌剂。有报告表明,对羟基苯甲酸酯可能与不孕症有关,这是由于它们对基础类固醇生成特性的影响或造成线粒体损伤的能力。尽管人们越来越担心对羟基苯甲酸酯是内分泌干扰物,但尚不清楚它们是否会在人体中影响这些作用,特别是在与环境相关的浓度下。在这项研究中,基于对孕酮生成以及关键类固醇生成基因( 、 、 和 )调控的评估,使用人颗粒细胞原代培养来评估类固醇生成。筛选了两种具有商业相关性的对羟基苯甲酸酯,即甲基对羟基苯甲酸酯(MPB)和丁基对羟基苯甲酸酯(BPB)的影响。将细胞暴露于从相对较低(典型环境暴露水平)到相对较高的多种浓度下。通过对羟基苯甲酸酯改变类固醇生成基因、孕酮或雌二醇生成以及对线粒体健康的影响来评估其作用,通过评估线粒体活性以及线粒体DNA含量来进行评估。MPB和BPB均未对孕酮生成或控制类固醇生成的基因表达产生任何影响。只有BPB影响线粒体,在超生理浓度(1000 nM)下降低线粒体DNA含量。长时间暴露于这些化合物对这些参数均无影响。总之,MPB和BPB均未显著影响颗粒细胞中的基础类固醇生成。尽管支持对羟基苯甲酸酯毒性的证据普遍存在,但在此我们提出证据表明,对羟基苯甲酸酯不会影响人颗粒细胞中的基础类固醇生成。