In light of the recent lead contamination of the water in Flint, Michigan and its potential adverse outcomes, much research and media attention has turned towards the safety profile of commonly used chelators. Dimercapto-1-propanesulfonic acid (DMPS) typically used in the treatment of lead, mercury and arsenic poisoning also displays a high affinity towards transition metals such as zinc and copper, essential for biological functioning. It is given in series of dosages (0.2-0.4g/day) over a long period, and has the ability to enter cells. In this work, we investigated the mechanism through which increasing concentrations of DMPS alter oocyte quality as judged by changes in microtubule morphology (MT) and chromosomal alignment (CH) of metaphase II mice oocyte. The oocytes were directly exposed to increasing concentration of DMPS (10, 25, 50, 100 and 300μM) for four hours (time of peak plasma concentration after administration) and reactive oxygen species (mainly hydroxyl radical and superoxide) and zinc content were measured. This data showed DMPS plays an important role in deterioration of oocyte quality through a mechanism involving zinc deficiency and enhancement of reactive oxygen species a major contributor to oocyte damage. Our current work, for the first time, demonstrates the possibility of DMPS to negatively impact fertility. This finding can not only help in counseling reproductive age patients undergoing such treatment but also in the development of potential therapies to alleviate oxidative damage and preserve fertility in people receiving heavy metal chelators.
Keywords: DMPS; Infertility; Oocyte quality; Reactive oxygen species; Zinc deficiency.
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