원문정보
초록
영어
BPA is an endocrine disruptor, has been investigated for its impact on male fertility in several species of animals and human. However, the underlining molecular mechanisms and possible health hazards of BPA exposure are still far from being well understood. Considering in vitro experimental model, we investigated the effects of BPA (0.0001 to 100 μM) exposure on spermatozoa. We demonstrated that BPA is capable of affecting several sperm functions by upregulating the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase-A (PKA) activity. High concentrations of BPA was also responsible for the activation of protein tyrosine phosphorylation in a PKA-dependent signaling subsequently induced a precocious acrosome reaction. Simultaneously, BPA has been found to compromise the rate of fertilization and early embryonic development. Proteomics investigation of spermatozoa reveled that BPA induced differential expressions of major sperm proteins that were responsible for the pathogenesis of many diseases. Considering in vivo experimental model, we studied the effects of gestational BPA exposure (environmental relevant doses) on non-capacitated/ capacitated spermatozoa in F1 adult mice. We demonstrated that BPA inhibited several sperm function in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased PKA activity and tyrosine phosphorylation (non-capacitated) in spermatozoa. We also noticed that BPA decreased average litter size as well as compromise the rates of cleavage and blastocyst formation. Proteins differentially expressed in capacitated/ non-capacitated spermatozoa play a critical role in energy metabolism, stress responses, and fertility finally predispose to the development of several diseases. On the basis of these results, both direct and gestational exposure to BPA alter spermatozoa function and the proteomic profile, ultimately affecting their fertility potential. Therefore, it is of critical public health significance to reevaluate the levels of BPA exposure that are currently deemed to be acceptable.
