RXFP2 as novel potential biomarker for abnormal differentiation induced by diethylstilbestrol in the gubernaculum of fetal mice.

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.