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. 2018 Dec 18;19(12):4097.
doi: 10.3390/ijms19124097.

Zinc: A Necessary Ion for Mammalian Sperm Fertilization Competency

Free PMC article

Zinc: A Necessary Ion for Mammalian Sperm Fertilization Competency

Karl Kerns et al. Int J Mol Sci. .
Free PMC article


The importance of zinc for male fertility only emerged recently, being propelled in part by consumer interest in nutritional supplements containing ionic trace minerals. Here, we review the properties, biological roles and cellular mechanisms that are relevant to zinc function in the male reproductive system, survey available peer-reviewed data on nutritional zinc supplementation for fertility improvement in livestock animals and infertility therapy in men, and discuss the recently discovered signaling pathways involving zinc in sperm maturation and fertilization. Emphasis is on the zinc-interacting sperm proteome and its involvement in the regulation of sperm structure and function, from spermatogenesis and epididymal sperm maturation to sperm interactions with the female reproductive tract, capacitation, fertilization, and embryo development. Merits of dietary zinc supplementation and zinc inclusion into semen processing media are considered with livestock artificial insemination (AI) and human assisted reproductive therapy (ART) in mind. Collectively, the currently available data underline the importance of zinc ions for male fertility, which could be harnessed to improve human reproductive health and reproductive efficiency in agriculturally important livestock species. Further research will advance the field of sperm and fertilization biology, provide new research tools, and ultimately optimize semen processing procedures for human infertility therapy and livestock AI.

Keywords: capacitation; fertility; fertilization; proteasome; sperm; zinc.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in this review; in the collection, analyses, or interpretation; in the writing of the manuscript, or in the decision to publish the results.


Figure 1
Figure 1
Summary of Zinc (Zn) signatures and free zinc ion (Zn2+) regulation of the fertilization competency of mammalian spermatozoa. (a) Super-resolution images of the non-capacitated boar sperm Zn signature 1 (a’) and acrosome-remodeled sperm Zn signature 3 (a'') acquired by the Leica TCP SP8 stimulated emission depletion (STED) microscope (free zinc ions in green, outer acrosomal membrane in cyan, remodeled sperm head plasma membrane in red; scale bars in gray: 5 μm). (a''') High Zn2+ concentration (2 mM) negatively regulates proton channel Hv1, responsible for the rise of intracellular pH, facilitating: (1) Ca2+ entry via CatSper and (2) protein tyrosine phosphorylation (pY), triggered by activation of soluble sperm adenylyl cyclase (SACY), increasing intracellular cAMP, activating protein kinase A (PKA) and phosphorylating protein tyrosine phosphatases (PTP) to an inactive state. For general capacitation pathway, review see Kerns et al., [144]). Following acrosome remodeling and exocytosis, zona pellucida (ZP) proteinases (acrosin, MMP2, and the 26S proteasome) implicated in endowing the spermatozoon with the ability to penetrate the ZP are activated. Zn2+, abundantly present in the fertilizing sperm triggered oocyte zinc shield, negatively regulates proteinase activities of spermatozoa bound to the zona or present in the perivitelline space, de-capacitating spermatozoa and serving as a newly proposed anti-polyspermy defense mechanism. (b) Capacitation-indicating state of the zinc signatures. Signature 1 spermatozoa are in a non-capacitated state. Signature 2 spermatozoa display hyperactivated motility. Only capacitating spermatozoa susceptible to progesterone (P4) chemoattraction exhibit chemorepulsion by Zn2+. Signature 3 spermatozoa exhibit acrosome remodeling while acrosomal exocytosis reportedly occurs in signature 4.

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