a Laboratory of Reproductive Toxicology, Department of Pharmacy , State University of Centro-Oeste , Parana , Brazil.
b Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina , Universidade Federal de São Paulo (Unifesp/EPM) , São Paulo , Brazil.
J Toxicol Environ Health A. 2019;82(3):163-175. doi: 10.1080/15287394.2019.1572557. Epub 2019 Feb 12.
Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) that is widely used in the manufacturing of plastics and inner linings of food cans. Previously, it was reported that BPA disturbed the sexual dimorphic nucleus of the hypothalamus and delaying the onset of puberty attributed to an estrogenic action. In addition, BPA during the perinatal period increased LH serum concentrations in male offspring of dams at doses below the reproductive NOAEL (No Observable Adverse Effect Level) based upon World Health Organization guidelines. Based upon these findings, the objective of this study was to (1) determine the effects of perinatal treatment with low doses of BPA on regulation of spermatogenesis in adult offspring and (2) elucidate molecular mechanisms involved in the pathogenesis of gonadal dysfunction. The expression of genes related to spermatogenesis was disrupted with adverse consequences on sperm production, reserves, and function. Both BPA treated groups exhibited reduction in sperm production and epithelial height of seminiferous tubules, accompanied by diminished integrity of the acrosome and plasma membrane, decreased mitochondrial activity and increased incidence of morphological abnormalities. The sperm transit time was also slower. However, only in the group receiving the higher BPA dose was transcript expression of genes affected (reduced Ar and increased Esr1). It is of interest that serum testosterone levels were elevated in the same group where Ar was decreased. Data suggest that exposure to low BPA doses during hypothalamic sexual differentiation period produces permanent deleterious effects on spermatogenesis in adulthood.
双酚 A（BPA）是一种内分泌干扰化学物质（EDC），广泛用于制造塑料和食品罐的内涂层。此前有报道称，BPA 会干扰下丘脑的性二态核，并延迟青春期的发生，这归因于雌激素作用。此外，根据世界卫生组织的指导方针，在围产期，低于生殖无观察不良效应水平（NOAEL）的剂量，BPA 会增加母体后代的 LH 血清浓度。基于这些发现，本研究的目的是：（1）确定围产期低剂量 BPA 处理对成年后代精子发生的调节作用；（2）阐明参与性腺功能障碍发病机制的分子机制。与精子发生相关的基因表达受到干扰，导致精子产生、储备和功能出现不良后果。两个 BPA 处理组均表现出精子产生减少和生精小管上皮高度降低，伴随着顶体和质膜完整性受损、线粒体活性降低以及形态异常发生率增加。精子通过时间也较慢。然而，只有在接受较高 BPA 剂量的组中，基因的转录表达受到影响（Ar 减少和 Esr1 增加）。有趣的是，在 Ar 减少的同一组中，血清睾酮水平升高。数据表明，在下丘脑性分化期间暴露于低剂量 BPA 会对成年期的精子发生产生永久性的有害影响。
