Duan Shouxing, Zhang Xuan, Jiang Xuewu, Xie Yao, Zheng Lian, Zhang Bingna, Xiao Wenfeng, Xie Xinquan, Xie Xiaojun, Li Jianhong, Ma Shuhua
Department of Pediatric Surgery, The First Affiliated Hospital of Shantou University Medical College No. 57 Changping Road, Shantou 515041, Guangdong, China.
Department of Pediatric Surgery, The Second Affiliated Hospital of Shantou University Medical College No. 69 Dongxiabei Road, Shantou 515041, Guangdong, China.
Am J Transl Res. 2020 Jul 15;12(7):3715-3727. eCollection 2020.
Environmental estrogens (EEs) have been correlated with abnormalities in the male urogenital system. However, the mechanism underlying the effect of these molecules remains unclear. In vitro and in vivo experiments were performed to examine the expression level and mechanism of relaxin family peptide receptor 2 (RXFP2) in the gubernaculum of fetal mice following diethylstilbestrol (DES) treatment. The in vivo results demonstrate that DES treatment increased the stillbirth rate gradually, decreased the gubernacular cone volume significantly, and disrupted the tissue structure, leading to incomplete testicular descent. In vitro experiments reveal that DES administration resulted in abnormal cellular morphology and structural disorder of gubernacular cells, which lost their original morphology in a dose-dependent manner. Moreover, DES-induced F-actin rearrangement and stress fiber formation in cultured cells. Protein quantitative analysis showed that the RXFP2 level in each experimental group was significantly lower than that of the normal group. In conclusion, DES affects the morphology and alters the gubernaculum structure, as well as the expression of RXFP2 protein. These data demonstrate that DES is toxic to gubernaculum in fetal mice, and that RXFP2 is associated with the abnormal gubernaculum morphology induced by DES. Taken together, these data suggest that RXFP2 may be a novel potential biomarker for abnormal differentiation of the gubernaculum.
环境雌激素（EEs）已被证实与男性泌尿生殖系统异常相关。然而，这些分子发挥作用的潜在机制仍不清楚。本研究通过体外和体内实验，检测己烯雌酚（DES）处理后胎鼠睾丸引带中松弛素家族肽受体2（RXFP2）的表达水平及机制。体内实验结果显示，DES处理使死产率逐渐升高，睾丸引带圆锥体积显著减小，组织结构遭到破坏，导致睾丸下降不全。体外实验表明，DES处理导致睾丸引带细胞形态异常和结构紊乱，细胞呈剂量依赖性失去原有形态。此外，DES可诱导培养细胞中F-肌动蛋白重排和应力纤维形成。蛋白质定量分析显示，各实验组中RXFP2水平均显著低于正常组。综上所述，DES影响睾丸引带形态，改变其结构以及RXFP2蛋白表达。这些数据表明，DES对胎鼠睾丸引带具有毒性作用，且RXFP2与DES诱导的睾丸引带形态异常有关。综合来看，这些数据提示RXFP2可能是睾丸引带异常分化的一种新型潜在生物标志物。
