Regulation and Distribution of Zinc in the Caenorhabditis elegans Reproductive System

Sue, Aaron Christopher

doi:https://doi.org/10.21985/n2-r733-9x05

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Regulation and Distribution of Zinc in the Caenorhabditis elegans Reproductive System

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Reproduction requires a complex orchestration of processes from the formation of the reproductive system through the successful development of the fetus, and nutrients are necessary to fuel these processes during many aspects of reproduction. Zinc is an essential metal that is fundamental in gamete maturation, gonadogenesis, and fertilization. Disruption in zinc levels leads to numerous defects, including meiotic errors, germline production, and embryo and fetal morphology. Thus, zinc must be carefully regulated both spatially and temporally to ensure the appropriate amount of zinc is available. This requirement has been observed in highly divergent species, and several zinc regulators and distributions have been identified. Caenorhabditis elegans shares a similar dependence on zinc, however the genes that regulate zinc in the reproductive system and the levels of zinc for portions of oocyte development have not been fully elucidated. We hypothesized that C. elegans would have conserved regulators of zinc in the oocyte, namely zinc transporters. Additionally, labile zinc accumulates as oocytes mature in worms. Using mammalian transporters as a guide, several C. elegans transporters were phylogenetically identified as potential zinc transporters involved in reproduction. We identified two putative zinc transporters, zipt-2.4 and zipt-15, that were critical for normal reproduction. Further examination of these genes identified morphological defects in the reproductive system, as well as expression patterns in both germline and non-germline cell types. These discoveries demonstrate that zinc regulation is critical for not just oocyte maturation, but tissue development as well. We also investigated how zinc is regulated on a systemic level by using fluorescent probes to visualize labile zinc distribution in the whole worm reproductive system. We developed a method for imaging labile zinc in vivo using the probe ZincBY-1 and found a gradient of labile zinc that increases in concentration as the oocyte matures. This observation agrees with mammalian studies, as well as complements the in vitro measurements made in worms. This methodology was used as a platform to study several novel zinc probes in a biological system. We demonstrated that C. elegans is a powerful tool to assess biological properties of metal probes. These techniques were also applied to further study the zinc redistribution following fertilization in worms. Together, these results demonstrate the advantages of using C. elegans as a model system for studying zinc in reproductive biology. The conservation of several observations between nematodes and mammals means that studies in nematodes could be used as guides for targeted approaches in humans. The genetic tractability, simple cell lineage, rapid development, and transparency allows for rapid exploration of reproductive phenomenon.

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