Departments of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Reprod Toxicol. 2023 Dec;122:108491. doi: 10.1016/j.reprotox.2023.108491. Epub 2023 Oct 19.
Phthalates are synthetic chemicals widely used as plasticizers and stabilizers in various consumer products. Because of the extensive production and use of phthalates, humans are exposed to these chemicals daily. While most studies focus on a single phthalate, humans are exposed to a mixture of phthalates on a regular basis. The impact of continuous exposure to phthalate mixture on uterus is largely unknown. Thus, we conducted studies in which adult female mice were exposed for 6 months to 0.15 ppm and 1.5 ppm of a mixture of phthalates via chow ad libitum. Our studies revealed that consumption of phthalate mixture at 0.15 ppm and 1.5 ppm for 6 months led to a significant increase in the thickness of the myometrial layer compared to control. Further investigation employing RNA-sequencing revealed an elevated transforming growth factor beta (TGF-β) signaling in the uteri of mice fed with phthalate mixture. TGF-β signaling is associated with the development of fibrosis, a consequence of excessive accumulation of extracellular matrix components, such as collagen fibers in a tissue. Consistent with this observation, we found a higher incidence of collagen deposition in uteri of mice exposed to phthalate mixture compared to unexposed controls. Second Harmonic Generation (SHG) imaging showed disorganized collagen fibers and nanoindentation indicated a local increase in uterine stiffness upon exposure to phthalate mixture. Collectively, our results demonstrate that chronic exposure to phthalate mixture can have adverse effects on uterine homeostasis.
邻苯二甲酸酯是一种广泛应用于各种消费品的合成化学物质，作为增塑剂和稳定剂。由于邻苯二甲酸酯的广泛生产和使用，人类每天都会接触到这些化学物质。虽然大多数研究都集中在单一的邻苯二甲酸酯上，但人类经常会接触到邻苯二甲酸酯的混合物。持续接触邻苯二甲酸酯混合物对子宫的影响在很大程度上是未知的。因此，我们进行了研究，成年雌性小鼠通过自由进食摄入 0.15ppm 和 1.5ppm 的邻苯二甲酸酯混合物，持续暴露 6 个月。我们的研究表明，与对照组相比，连续 6 个月摄入 0.15ppm 和 1.5ppm 的邻苯二甲酸酯混合物会导致子宫肌层厚度显著增加。进一步采用 RNA 测序的研究揭示了喂食邻苯二甲酸酯混合物的小鼠子宫中转化生长因子β（TGF-β）信号的升高。TGF-β信号与纤维化的发展有关，纤维化是组织中细胞外基质成分（如胶原纤维）过度积累的结果。与这一观察结果一致，我们发现暴露于邻苯二甲酸酯混合物的小鼠子宫中胶原沉积的发生率明显高于未暴露的对照组。二次谐波产生（SHG）成像显示胶原纤维排列紊乱，纳米压痕表明暴露于邻苯二甲酸酯混合物后子宫硬度局部增加。总的来说，我们的结果表明，慢性接触邻苯二甲酸酯混合物会对子宫内环境产生不良影响。
