Tris (4-hydroxyphenyl)ethane (THPE), a trisphenol compound widely used as a branching agent and raw material in plastics, adhesives, and coatings is rarely regarded with concern. However, inspection of in vitro data suggests that THPE is an antagonist of estrogen receptors (ERs). Accordingly, we aimed to evaluate the antiestrogenicity of THPE in vivo and tested its effect via oral gavage on pubertal development in female CD-1 mice. Using uterotrophic assays, we found that THPE either singly, or combined with 17β-estradiol (E₂) (400 μg/kg bw/day) suppressed the uterine weights at low doses (0.1, 0.3, and 1 mg/kg bw/day) in 3-day treatment of weaning mice. When mice were treated with THPE during adolescence (for 10 days beginning on postnatal day 24), their uterine development was significantly retarded at doses of at least 0.1 mg/kg bw/day, manifest as decreased uterine weight, atrophic endometrial stromal cells and thinner columnar epithelial cells. Transcriptome analyses of uteri demonstrated that estrogen-responsive genes were significantly downregulated by THPE. Molecular docking shows that THPE fits well into the antagonist pocket of human ERα. These results indicate that THPE possesses strong antiestrogenicity in vivo and can disrupt normal female development in mice at very low dosages.

三（4-羟苯基）乙烷（THPE）是一种三酚化合物，广泛用作塑料，胶粘剂和涂料中的支化剂和原料，很少引起人们的关注。但是，对体外数据的检查表明THPE是雌激素受体（ER）的拮抗剂。因此，我们旨在评估体内THPE的抗雌激素性，并通过口服管饲法测试其对雌性CD-1小鼠青春期发育的作用。使用子宫营养试验，我们发现THPE单独或与17β-雌二醇（E ₂）（400μg/ kg bw /天）在3天的断奶小鼠治疗中以低剂量（0.1、0.3和1 mg / kg bw /天）抑制了子宫重量。在青春期（从出生后第24天开始的10天）中用THPE治疗小鼠时，其子宫发育在至少0.1 mg / kg bw / day的剂量下明显受阻，表现为子宫重量减少，萎缩性子宫内膜间质细胞变薄柱状上皮细胞。子宫的转录组分析表明，THPE显着下调了雌激素反应基因。分子对接表明THPE非常适合人ERα的拮抗剂口袋。这些结果表明，THPE在体内具有很强的抗雌激素性，并且可以以非常低的剂量破坏小鼠的正常雌性发育。