Reproductive toxicity of intrauterine exposure to 2，3，7，8-tetrachlorodibenzo-p-dioxin in male offspring rats

Abstract:

Objective：To investigate the effect and mechanism of action of 2，3，7，8-tetrachlorodibenzo-p-dioxin（TCDD） intrauterine exposure on the reproductive function of male offspring rats. Methods：After mating，pregnant rats were randomly divided into high-dose TCDD group（0.5 μg/kg），low-dose TCDD group（0.1 μg/kg），and solvent control group，with 6 rats in each group. The TCDD groups and the control group were treated with TCDD and corn oil，respectively，by intragastric administration on gestation days 8-14 （GD8-14）. After being delivered naturally，male offspring were measured for anogenital distance（AGD），and testicular organ coeffi－cient was also calculated. Then the quality and quantity of sperm were analyzed by a sperm quality analyzer. In addition，the level of testosterone（T） in the serum of male offspring was determined by enzyme-linked immunosorbent assay，and the expression levels of the apoptosis-related proteins Bax，Bcl2，and caspase-3 were also measured. Results：Compared with the control group，both the low-dose group and high-dose group had a significantly shortened AGD[（1.32±0.01） cm and （1.21±0.02） cm vs. （1.49±0.04） cm，P=0.000]，and these two groups showed significant reductions in sperm count[（63.67±3.44）×106/mL and （45.33±5.47）×106/mL vs. （72.33±4.46）×106/mL] and sperm motility rate[（64.40±3.14）% and （53.87±3.65）% vs. （78.53±1.26）%]. Furthermore，a signifi－cantly increased rate of sperm deformity[（4.83±0.75）% and （8.00±1.10）% vs. （2.17±0.75）%，P=0.000] and a significantly decreased level of testosterone in serum[（2.38±0.08） ng/mL and （2.10±0.09） ng/mL vs. （2.68±0.06） ng/mL，P=0.000] were also observed in these two groups. The testicular weight and testicular organ coefficient in the high-dose group decreased significantly compared with those in the low-dose group（P=0.001 and 0.004，respectively）. With an increase in TCDD dose，the relative expression level of Bax protein increased significantly in testic－ular tissue cells（0.836±0.004 vs. 1.185±0.004 vs. 1.414±0.001，P=0.000），whereas the expression level of Bcl-2 demonstrated an opposite trend（1.368±0.053 vs. 1.108±0.040 vs. 0.751±0.022，P=0.001）. Meanwhile，the high-dose group had a significant reduc－tion in the expression level of pro-caspase-3 and a significant increase in the expression level of cleaved-caspase-3（P=0.000）. Conclusion：Intrauterine exposure to TCDD can induce feminization of male offspring，affect their fertility，and cause reproductive toxicity. The mechanism may be related to cell proliferation-apoptosis imbalance and activation of the mitochondrial pathway of apop－tosis in the testicular tissue cells of these offsprings.