The aims of this study were to examine the effects of CdCl2 on the viability, migration and cytoskeleton of cultured mouse TM4 Sertoli cells. Time-and concentration-dependent changes were exhibited by the cells but 1 µM CdCl2 was sub-cytotoxic at all time-points. Exposure to 1 and 12 µM CdCl2 for 4 h resulted in disruption of the leading edge, as determined by chemical staining. Cell migration was inhibited by both 1 and 12 µM CdCl2 in a scratch assay monitored by live cell imaging, although exposure to the higher concentration was associated with cell death. Western blotting and immunofluorescence staining indicated that CdCl2 caused a concentration dependent reduction in actin and tubulin levels. Exposure to Cd 2+ also resulted in significant changes in the levels and/or phosphorylation status of the microtubule and microfilament destabilising proteins cofilin and stathmin, suggesting disruption of cytoskeletal dynamics. Given that 1-12 µM Cd 2+ is attainable in vivo, our findings are consistent with the possibility that Cd 2+ induced impairment of testicular development and reproductive health may involve a combination of reduced Sertoli cell migration and impaired Sertoli cell viability depending on the timing, level and duration of exposure.

Exposure of the fetal testis to numerous individual environmental chemicals is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, ‘real-life’ exposure involves complex mixtures of environmental chemicals (ECs). Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage). Fetal testes from continuously exposed ewes were either unaffected at Day 80 or exhibited a reduced area of testis immunostained for CYP17A1 protein at Day 140. Fetal testes from Day 140 pregnant ewes exposed transiently for 80 day periods during early (0-80 days), mid (30-110 days) or late (60-140 days) pregnancy, had fewer Sertoli cells and reduced testicular area stained for CYP17A1. Male fetuses from ewes exposed during late pregnancy also exhibited reduced fetal body, adrenal and testis mass, anogenital distance and lowered testosterone: collectively indicative of an anti-androgenic effect. Exposure limited to early gestation induced more testis transcriptome changes than observed for continuously exposed Day 140 fetuses. These data suggest that a short period of EC exposure does not allow sufficient time for the testis to adapt. Consequently, testicular transcriptomic changes induced during the first 80 days of gestation may equate with phenotypic effects observed at Day 140. In contrast, relatively fewer changes in the testis transcriptome in fetuses exposed continuously to ECs throughout gestation is associated with less severe consequences. Unless corrected by or during puberty, these differential effects would predictably have adverse outcomes for adult testicular function and fertility.

Antimicrobial resistance (AMR) has become one of the more serious threats to the global health. The emergence of bacteria resistant to antimicrobial substances decreases the potencies of current antibiotics. Consequently, there is an urgent and growing need for the developing of new classes of antibiotics. Three prepared novel iron complexes have a broad-spectrum antimicrobial activity with minimum bactericidal concentration (MBC) values ranging from 3.5 to 10 mM and 3.5 to 40 mM against Gram-positive and Gram-negative bacteria with antimicrobial resistance phenotype, respectively. Time-kill studies and quantification of the extracellular DNA confirmed the bacteriolytic mode of action of the iron-halide compounds. Additionally, the novel complexes showed significant antibiofilm activity against the tested pathogenic bacterial strains at concentrations lower than the MBC. The cytotoxic effect of the complexes on different mammalian cell lines show sub-cytotoxic values at concentrations lower than the minimum bactericidal concentrations.

Antimicrobial resistance (AMR) has become one of the more serious threats to the global health. The emergence of bacteria resistant to antimicrobial substances decreases the potencies of current antibiotics. Consequently, there is an urgent and growing need for the developing of new classes of antibiotics. Three prepared novel iron complexes have a broad-spectrum antimicrobial activity with minimum bactericidal concentration (MBC) values ranging from 3.5 to 10 mM and 3.5 to 40 mM against Gram-positive and Gram-negative bacteria with antimicrobial resistance phenotype, respectively. Time-kill studies and quantification of the extracellular DNA confirmed the bacteriolytic mode of action of the iron-halide compounds. Additionally, the novel complexes showed significant antibiofilm activity against the tested pathogenic bacterial strains at concentrations lower than the MBC. The cytotoxic effect of the complexes on different mammalian cell lines show sub-cytotoxic values at concentrations lower than the minimum bactericidal concentrations.

A neutral octahedral mononuclear iron(II) tetrabromide complex, [Fe(Hampy)₂Br₄], that consists of equatorial bromide and protonated aminopyrazinium axial ligands is successfully synthesised through redox chemistry and analysed using X-ray crystallography. The iron(II) oxidation state is balanced by the protonated pyrazinium nitrogen just outside the coordination sphere. The biological properties of this and two other related complexes are investigated using both Gram-negative and Gram-positive bacteria as well as methicillin resistant strains. They all exhibit some antimicrobial properties albeit at moderate to poor concentrations. However, the tetrahalide complexes analysed exhibit excellent anti biofilm properties well below cytotoxic levels.