Abstract
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.
Highlights
Encyclopedism of Biological ZincZinc (Zn) is one of the most highly abundant elements on earth, an essential micronutrient to all things living, typically occurring as a divalent cation metal with moderate reactivity and reducing properties
While ancient Etruscans and Romans may have already recognized medicinal properties of zinc salts [7], its biological importance was only fully realized in the 19th century, and it entered the mainstream human medicine hundred years later, when the first studied were conducted on dwarfism, human zinc deficiency, and general importance of zinc as a growth factor [8]
We previously reported the presence of a ring finger ubiquitin ligase homologous to UBR7 in round spermatids and spermatozoa [106], and implicated this zinc finger containing enzyme in spermiogenesis and possibly in the proteolytic degradation of the zona pellucida (ZP) at fertilization [107]
Summary
Zinc (Zn) is one of the most highly abundant elements on earth, an essential micronutrient to all things living, typically occurring as a divalent cation metal with moderate reactivity and reducing properties. Essential biological roles of zinc include signaling, enzymatic activities, regulation of normal growth and sexual maturation, digestion, homeostasis of central nervous system, and mitochondrial oxidative stress [1,2]. There are two families of proteins that are responsible for the movement of Zn2+ through biological membranes, exercising sustained homeostatic control These include zinc-importer (ZIP; Zrt-, Irt-like) family proteins that transport Zn2+ into the cytosol and the zinc transporter (ZnT) family proteins transporting Zn2+ out of the cytosol [20]. We review 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 recently discovered signaling pathways involving zinc in sperm maturation and fertilization
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