Li Xiaoheng, Chen Xiaomin, Hu Guoxin, Li Linxi, Su Huina, Wang Yiyan, Chen Dongxin, Zhu Qiqi, Li Chao, Li Junwei, Wang Mingcang, Lian Qingquan, Ge Ren-Shan
The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Department of Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325000, China.
Int J Environ Res Public Health. 2016 Feb 23;13(3):246. doi: 10.3390/ijerph13030246.
Dicyclohexyl phthalate (DCHP) is one of the phthalate plasticizers. The objective of the present study was to investigate the effects of DCHP on fetal Leydig cell distribution and function as well as testis development. Female pregnant Sprague Dawley dams orally received vehicle (corn oil, control) or DCHP (10, 100, and 500 mg/kg/day) from gestational day (GD) 12 to GD 21. At GD 21.5, testicular testosterone production, fetal Leydig cell number and distribution, testicular gene and protein expression levels were examined. DCHP administration produced a dose-dependent increase of the incidence of multinucleated gonocytes at ≥ 100 mg/kg. DCHP dose-dependently increased abnormal fetal Leydig cell aggregation and decreased fetal Leydig cell size, cytoplasmic size, and nuclear size at ≥ 10 mg/kg. DCHP reduced the expression levels of steroidogenesis-related genes (including Star, Hsd3b1, and Hsd17b3) and testis-descent related gene Insl3 as well as protein levels of 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) and insulin-like 3 (INSL3) at ≥ 10 mg/kg. DCHP significantly inhibited testicular testosterone levels at ≥ 100 mg/kg. The results indicate that in utero exposure to DCHP affects the expression levels of fetal Leydig cell steroidogenic genes and results in the occurrence of multinucleated gonocytes and Leydig cell aggregation.
邻苯二甲酸二环己酯（DCHP）是一种邻苯二甲酸酯类增塑剂。本研究的目的是调查DCHP对胎儿睾丸间质细胞分布和功能以及睾丸发育的影响。雌性Sprague Dawley怀孕母鼠从妊娠第12天至第21天经口给予赋形剂（玉米油，对照组）或DCHP（10、100和500 mg/kg/天）。在妊娠第21.5天，检测睾丸睾酮生成、胎儿睾丸间质细胞数量和分布、睾丸基因和蛋白质表达水平。给予≥100 mg/kg的DCHP会导致多核生殖细胞发生率呈剂量依赖性增加。给予≥10 mg/kg的DCHP会使异常胎儿睾丸间质细胞聚集呈剂量依赖性增加，并使胎儿睾丸间质细胞大小、细胞质大小和细胞核大小减小。给予≥10 mg/kg的DCHP会降低类固醇生成相关基因（包括Star、Hsd3b1和Hsd17b族）和睾丸下降相关基因Insl3的表达水平，以及3β-羟基类固醇脱氢酶1（HSD3B1）和胰岛素样3（INSL3）的蛋白质水平。给予≥100 mg/kg的DCHP会显著抑制睾丸睾酮水平。结果表明，子宫内暴露于DCHP会影响胎儿睾丸间质细胞类固醇生成基因的表达水平，并导致多核生殖细胞的出现和睾丸间质细胞聚集。
