Reproductive toxicology of nickel – Review

Abstract

The goal of this minireview is to summarize our current knowledge on the reproductive toxicity of soluble nickel salts. We made an attempt to present the most relevant data obtained from in vivo and in vitro experiments performed on mammals, mammalian primary cell cultures and cell lines. Nickel has been demonstrated to disturb the mammalian reproductive functions at several levels of regulation. The results of previous investigations indicate that the hormonal effects may play an important role in the reproductive toxicology of nickel both at the neuroendocrine and gonadal levels in the hypothalamic-pituitary-gonadal (HPG) axis. At the molecular level, it may be important that nickel may substitute certain other metals in metal dependent enzymes, leading to an altered protein function. It readily crosses the cell membrane via calcium channels and competes with calcium for specific receptors. Nickel can cross-link aminoacids to DNA, lead to formation of reactive oxygen species (ROS), moreover mimic hypoxia. These changes may lead to the activation of some signaling pathways, subsequent transcription factors and eventually to alterations in gene expression and cellular metabolism. These events are likely to be involved in the reproductive toxicity of nickel.

Effects of Metallic Elements on Reproduction and Development

“…Qualitative analysis revealed dilatation of the blood vessels in the interstitium, undulation of the basal membrane, and several empty spaces in the germinal epithelium. A specific assay detected a higher frequency of localized apoptosis in the interstitium of Ni-administered animals compared to controls (Forgacs et al, 2012).…”

Possible implications of Ni(II) on oral IL-1β-induced inflammatory processes

“…Different authors analyzed Ni-induced mechanism in vitro and in vivo using several cell types (immune cells like dendritic cells (DCs) or monocytes, cancer cell lines or epithelial cells of the lung, dermis or gingival) various Ni(II) concentrations and analysis methods [5,[14][15][16][17][18][19][20]39]. In almost every cell line, Ni(II) induced dose-and time-dependent changes of proand anti-inflammatory cytokines or other mediators such as prostaglandins or MMPs [5,[14][15][16][17][18][19][20]39].…”

“…Thereby, biocompatibility is related to the duration and route of exposure, form and concentration of this metal. Several studies investigated the impact of Ni(II) on cell metabolism using immune cells like monocytes and dendritic cells (DCs) as well as human dermal or gingival epithelial cells [5,[14][15][16][17][18][19][20]. The authors detected dose-and time-depended cytotoxic and pro-inflammatory reactions.…”

Níquel en alimentos y factores influyentes en sus niveles, ingesta, biodisponibilidad y toxicidad: una revisión

“…Se ha visto que este metal atraviesa fácilmente la membrana celular a través de los canales de calcio, compitiendo con éste por los receptores específicos. También se ha visto que el níquel (Ni 2+ ) es capaz de imitar la hipoxia, lo que puede conducir a la activación de algunas vías de señalización y la transcripción posterior de sus factores, produciéndose eventualmente la alteración de la expresión génica y del metabolismo celular, y como consecuencia la génesis de toxicidad reproductiva y carcinogénesis (Forgacsa, Massányib, Lukacb, & Somosyc, 2012).…”