Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
J Hazard Mater. 2022 Aug 15;436:129213. doi: 10.1016/j.jhazmat.2022.129213. Epub 2022 May 24.
Humans are simultaneously and constantly exposed to various lipophilic chain phthalate acid esters. The association of urinary phthalate metabolites with altered male steroid hormone synthesis and metabolism was examined using epidemiology and toxicology studies. We measured 8 phthalate metabolites [monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-n-octylphthalate (MOP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP)] and two sex hormones [testosterone (T) and estradiol (E)] in single serum and repeated spot urine samples among 451 reproductive-age males. Moreover, in vitro experiments with Leydig cell MLTC-1 steroidogenesis and liver cell HepG2 efflux in response to mixed and individual phthalates were designed to simulate real-world scenarios of human exposure. As a joint mixture, the phthalate metabolite was inversely associated with serum T and E concentrations but positively associated with urinary T and E concentrations. Combined with in vitro experiments, DEHP metabolites were identified as the predominant contributor to the decline in hormone synthesis, and ATP-binding cassette (ABC) gene activation might be involved in hormone excretion. Exposure to environmentally relevant phthalates was associated with both altered steroid synthesis and excretion, which provides additional insights into the endocrine-disrupting potential of phthalates.
人类同时且持续地暴露于各种脂溶性邻苯二甲酸酯链酸酯中。本研究通过流行病学和毒理学研究，探讨了尿邻苯二甲酸代谢物与改变的男性甾体激素合成和代谢之间的关联。我们测量了 8 种邻苯二甲酸代谢物[邻苯二甲酸单甲酯（MMP）、邻苯二甲酸单乙酯（MEP）、邻苯二甲酸单丁酯（MBP）、邻苯二甲酸单苄酯（MBzP）、邻苯二甲酸单正辛酯（MOP）、邻苯二甲酸单（2-乙基己基）酯（MEHP）、邻苯二甲酸单（2-乙基-5-羟基己基）酯（MEHHP）和邻苯二甲酸单（2-乙基-5-氧代己基）酯（MEOHP）]和 2 种性激素[睾酮（T）和雌二醇（E）]在 451 名生殖期男性的单次血清和重复点尿样本中。此外，还设计了 Leydig 细胞 MLTC-1 类固醇生成和肝细胞 HepG2 外排的体外实验，以模拟人类暴露的真实情况。作为一种混合混合物，邻苯二甲酸代谢物与血清 T 和 E 浓度呈负相关，与尿 T 和 E 浓度呈正相关。结合体外实验，鉴定出 DEHP 代谢物是导致激素合成下降的主要因素，而三磷酸腺苷结合盒（ABC）基因的激活可能参与了激素排泄。暴露于环境相关的邻苯二甲酸酯与甾体激素合成和排泄的改变有关，这为邻苯二甲酸酯的内分泌干扰潜力提供了更多的见解。
