A novel approach to assessing bisphenol-A hazards using an in vitro model system

Abstract

BackgroundAlthough the toxicological impacts of the xenoestrogen bisphenol-A (BPA) have been studied extensively, but the mechanism of action is poorly understood. Eventually, no standard method exists for evaluating the possible health hazards of BPA exposure. Considering mice spermatozoa as a potential in vitro model, we investigated the effects of BPA exposure (0.0001, 0.01, 1, and 100 μM for 6 h) on spermatozoa and the related mechanisms of action. The same doses were also employed to evaluate protein profiles of spermatozoa as a means to monitor their functional affiliation to diseases.ResultsOur results demonstrated that high concentrations of BPA negatively affect sperm motility, viability, mitochondrial functions, and intracellular ATP levels by activating the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase-A pathways. Moreover, short-term exposure of spermatozoa to high concentrations of BPA induced differential expressions of 24 proteins. These effects appeared to be caused by protein degradation and phosphorylation in spermatozoa. Proteins differentially expressed in spermatozoa from BPA treatment groups are putatively involved in the pathogenesis of several diseases, mainly cancer, carcinoma, neoplasm, and infertility.ConclusionsBased on these results, we propose that BPA adversely affects sperm function by the activation of several kinase pathways in spermatozoa. In addition, BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa, subsequently involve in the pathogenesis of many diseases. Therefore, we anticipated that current strategy might broadly consider for the health hazards assessment of other toxicological agents.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2979-5) contains supplementary material, which is available to authorized users.

Long-term exposure to very low doses of bisphenol S affects female reproduction

“…This observation confirms the likelihood of BPS-mediated disruption of epigenetic modulation. In addition to steroidogenesis and epigenetics, cytoskeletal and associated factors (tubulin α-1B chain, talin-1, Ser/Thr-protein phosphatase 2A) are affected and considerably affiliated with other findings on cytoskeletal structures, accordingly with previous studies on BPA (Rahman et al 2016).…”

New Biological Insights on X and Y Chromosome-Bearing Spermatozoa

“…Different parts of the female reproductive tract, such as the uterus, uterotubal junction, and oviduct, are specifically programmed to select only a functionally mature spermatozoon for fertilization (Holt and Fazeli, 2010). Once the spermatozoa reach the oviduct, they temporarily attach to the isthmus epithelium to undergo capacitation before ovulation (Rahman et al, 2015(Rahman et al, , 2016. Capacitation is a process during which complex molecular, biochemical, and physiological changes occur in spermatozoa in the female reproductive tract or in in vitro specialized media and is a prerequisite for fertilization (Salicioni et al, 2007;Visconti, 2012;Kwon et al, 2015).…”

“…Identification and quantification of genes/proteins in a cell provides fascinating insights regarding their cellular functions. Genomics deals with the structure, function, evolution, and mapping of genomes (Bader et al, 2003), whereas proteomics involves novel approaches for characterizing proteins by performing qualitative and quantitative analyses (Rahman et al, 2016(Rahman et al, , 2017a(Rahman et al, , 2018. A spermatozoon provides half of the nuclear genetic material to the diploid offspring via fertilization.…”

Bisphenol A Affects on the Functional Properties and Proteome of Testicular Germ Cells and Spermatogonial Stem Cells in vitro Culture Model

“…Previous studies have shown that BPA, at both high and low concentrations, has marked effects on growth, maintenance and apoptosis related signaling in various cell types, including male germ cells 10 – 13 . Moreover, BPA has been shown to have vertically transferred effects on spermatozoa of F1 mice following exposure in gestational period 14 , and effects on spermatozoa in vitro 15 .…”