Endocrine disrupting compounds exposure and testis development in mammals

In the last few decades, there is substantial evidence that male reproductive function is deteriorating in humans and wildlife and this is associated with unintentional exposure to widely used synthetic chemicals. Subsequently, much has been done to show that certain chemicals in the environment adversely interfere with the developing fetal gonads of the laboratory animals. Some in vitro studies have demonstrated treatment-induced reproductive problems in offspring exposed to endocrine disrupting compounds (EDC) which are similar to those observed in wildlife and human population. Few EDC studies have demonstrated that there are certain periods of gestation when the developing fetus is highly sensitive and at risk of small endocrine changes. Similar observations have been made in the sewage sludge model, however, while animal studies have been insightful in providing valuable information about the range of effects that can be attributed to in utero exposure to EDCs, varying levels of maternal doses administered in different studies exaggerated extrapolation of these results to human. Thus the EDC concentration representative of fetal exposure levels is uncertain because of the complexities of its nature. So far, the level of fetal exposure can only be roughly estimated. There is substantial evidence from animal data to prove that EDCs can adversely affect reproductive development and function in male and more has accumulated on the mechanisms by which they exert their effects. This paper therefore, reviews previous studies to highlight the extent to which testis development can be disrupted during fetal life

Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures

Acknowledgements We thank George Corsar and Jim MacDonald for the management of experimental animals Funding This work was supported by the European Commission Framework 7 Programme (Contract No 212885)Peer reviewedPublisher PD

Sub-lethal concentrations of CdCl2 disrupt cell migration and cytoskeletal proteins in cultured mouse TM4 Sertoli cells

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 Cd2+ 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 Cd2+ is attainable in vivo, our findings are consistent with the possibility that Cd2+ 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

Retinal pigment epithelial cells can be cultured on fluocinolone acetonide treated nanofibrous scaffold

Engineered tissue currently lacks requisite capacity to sustain cell viability and functionality. Here we demonstrate that human RPE cell lines (ARPE-19) can be cultured on ultrathin suspended electrospun nanofibre scaffolds (ENS) composed of hydrophobic polymer polyacrylonitrile (PAN) and a water-soluble aliphatic diamine, without (untreated) or with (treated) fluocinolone acetonide (FA). Cells survived and retained their characteristic morphology for up to 150 days with FA-treated ENS and manifested a morphological epithelial phenotype with expression of biomarkers critical for maintaining retinal physiological characteristics. This novel technique for producing culture substrates provides suitable hydrophilicity and a protective environment for prolonged RPE culture and has immense potential for subretinal transplantation. The findings indicate that FA-treated ENS is an excellent matrix for retaining the differentiated and epithelial phenotype.</p

Expanding the family of tetrahalide iron complexes: synthesis, structure and biological applications

A neutral octahedral mononuclear iron(II) tetrabromide complex, [Fe(HaAmpy)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