Functional and Proteomic Alterations of F1 Capacitated Spermatozoa of Adult Mice Following Gestational Exposure to Bisphenol A

Abstract

Studies regarding bisphenol A (BPA) exposure and male (in)fertility have conventionally focused on modifications in ejaculated spermatozoa function from exposed individuals. However, mammalian spermatozoa are incapable of fertilization prior to achieving capacitation, the penultimate step in maturation. Therefore, it is necessary to investigate BPA-induced changes in capacitated spermatozoa and assess the consequences on subsequent fertilization. Here, we demonstrate the effect of gestational BPA exposure (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on the functions, biochemical properties, and proteomic profiles of F1 capacitated spermatozoa from adult mice. The data showed that high concentrations of BPA inhibited motility, motion kinematics, and capacitation of spermatozoa, perhaps because of increased lipid peroxidation and protein tyrosine nitration, and decreased intracellular ATP levels and protein kinase-A activity in spermatozoa. We also found that BPA compromised the rates of fertilization and early embryonic development. Differentially expressed proteins identified between BPA-exposed and control groups play a critical role in energy metabolism, stress responses, and fertility. Protein function abnormalities were responsible for the development of several diseases according to bioinformatics analysis. On the basis of these results, gestational exposure to BPA may alter capacitated spermatozoa function and the proteomic profile, ultimately affecting their fertility potential.

New Biological Insights on X and Y Chromosome-Bearing Spermatozoa

“…Thus, a 55 µm long spermatozoon efficiently covers 1000-3000 µm. During this journey, the morphology and chemotaxis of spermatozoa and ionic factors, protein phosphorylation (especially tyrosine), ATP, cyclic adenosine monophosphate, protein kinase-A (PKA), enzymatic factors, seminal plasma factors, and calcium ions present in spermatozoa play a dynamic role in keeping the spermatozoa motile (Kwon et al, 2014b;Rahman et al, 2017bRahman et al, , 2018. Simultaneously, certain fascinating physiological processes such as capacitation and the acrosome reaction occur in spermatozoa (Visconti, 2009;Battistone et al, 2013;Rahman et al, 2017b).…”

“…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 and Male Reproductive System

“…In additional, a significant increase in DNA damage to spermatocytes and decrease sperm count and motility was observed, following 12 weeks of BPA (10mg/kg bwt) administration in mice (44). Smilarly, Rahman et al (2017) reported that, toxic effect of gestational BPA exposure (5 mg/kg, and 50 mg/kg bw/day) on motility, capacitation, and motion kinematics of spermatozoa in mice. However, no or minimal effects were observed in the low-dose (50 µg/ kg) BPA group (45).…”

“…Smilarly, Rahman et al (2017) reported that, toxic effect of gestational BPA exposure (5 mg/kg, and 50 mg/kg bw/day) on motility, capacitation, and motion kinematics of spermatozoa in mice. However, no or minimal effects were observed in the low-dose (50 µg/ kg) BPA group (45). Detrimental effects of BPA on sperm quality showed in experimental animal models has been confirmed by some studies conducted among groups of BPA-exposed human males (46).…”

Endocrine Disruptors: Very Low Doses with Genuinely High Impacts on Male Reproduction

“…The comparable effect of EDs is known during spermatogenesis: BPA is capable of affecting meiotic division and chromosome segregation, increasing the incidence of aneuploidy-derived disorders [73]. In addition, the molecular mechanism of BPA consists in impacting several signal pathways and results in the change of protein kinase A activity and protein tyrosine phosphorylation, ATP generation, and oxidative stress-related enzymes (i.e., peroxiredoxin-5, glutathione peroxidase 4, succinate dehydrogenase), crucial for sperm motility and ability of oocyte fertilization [26,27,74]. Dose-response association of BPA and motility parameters of human sperm has been observed [75].…”