Prenatal exposure to diaethylstilbestrol in the rat inhibits transabdominal testicular descent with involvement of the INSL3/LGR8 system and HOXA10

Background Prenatal exposure to diaethylstilbestrol （DES） has been found to lead to intra-abdominal cryptorchidism, but the mechanism is still not completely clear. This study investigated the roles of the INSL3/LGR8 system and HOXA10 in DES-induced intra-abdominal cryptorchidism （DIIAC）. The effect of DES on steroidogenic factor-1 （SF-1）, that has been reported to control transcription of insulin-like factor 3 （INSL3）, was also investigated. Methods Fifty pregnant female SD rats at embryonic day 13.5 （E13.5） were randomly assigned to five groups that received a subcutaneous injections of dimethyl sulfoxide （control）, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, or 20 mg/kg of DES. Male offspring were sacrificed at E19.5, and fetal mortality and the degree of transabdominal testicular ascent （DTA） were determined under a stereomicroscope. The mRNA expression of INSL3 and SF-1 in the testis and leucine rich repeat-containing G protein-coupled receptors 8 （LGR8） and homeobox-A10 （HOXA10） in the gubemaculum were determined by RT-PCR. The expression of INSL3 protein was determined by Western blotting. Results Higher fetal mortality and DTA were induced by DES in a dose-dependent manner （P 〈0.01）. Compared with the control group, the expression of INSL3 and SF-1 mRNA were down-regulated in a dose-dependent manner （P 〈0.01） as was INSL3 protein; HOXA10 in the 2.5 mg/kg group and LGR8 mRNA in the 2.5 mg/kg and 5 mg/kg groups were not significantly different （P 〉0.05）; HOXA10 mRNA in groups C, D, and E decreased significantly and LGR8 mRNA levels in groups D and E increased significantly （P 〈0.05, P 〈0.01, respectively）. Conclusions DES can inhibit transabdominal testicular descent in a dose-dependent manner via down-regulating the expression of INSL3, which is induced by down-regulating the expression of SF-1. HOXA10 may not be involved in DES induced intra-abdominal cryptorchidism at 2.5 mg/kg, but is involved at 5, 10 and 20 mg/kg. LGR8 may not be responsible for DES-induced transabdominal testicular maldescent.