Lead and cadmium exposure induces male reproductive dysfunction by modulating the expression profiles of apoptotic and survival signal proteins in tea -garden workers

The aim of this study was to evaluate the impact of Lead (Pb) and Cadmium (Cd) exposure at the molecular level on the reproductive status of tea garden workers in North-East India. Using semen samples, we experimentally determined sperm analysis as well as oxidative stress parameters in all samples and evaluated the expression levels of apoptotic and cell survival proteins [p53, phospho-Akt, nuclear factor-kappa B (NF-kappa B, p50 subunit) and B cell lymphoma 2 (Bcl2)]. Our data revealed significant differences in the average heavy metal concentrations and various semen analysis profile between the infertile and normal groups. Increasing Pb and Cd concentrations in semen samples of patients showed positive associations with increasing number of multiple defects in sperm and the level of seminal oxidative stress markers in the high Pb and Cd concentration groups. These groups also exhibited positive correlations between high metal concentrations and the average p53 expression levels, but negative correlations with the mean p-Akt cascade protein levels in sperm cells. In the low Pb and Cd concentrations groups, we also observed reverse mean range and correlation patterns. Therefore, our findings may suggest that graded levels of metal exposure significantly influence the relative fluctuation in the levels of p53 and Akt cascade proteins in the sperm cells of infertile subjects. Furthermore, this may be a regulating factor of sperm cell fate, in turn, determining the fertility outcome of the men working in the tea gardens.