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      Role of Zinc (Zn) in Human Reproduction: A Journey from Initial Spermatogenesis to Childbirth

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          Abstract

          Zinc (Zn), the second-most necessary trace element, is abundant in the human body. The human body lacks the capacity to store Zn; hence, the dietary intake of Zn is essential for various functions and metabolism. The uptake of Zn during its transport through the body is important for proper development of the three major accessory sex glands: the testis, epididymis, and prostate. It plays key roles in the initial stages of germ cell development and spermatogenesis, sperm cell development and maturation, ejaculation, liquefaction, the binding of spermatozoa and prostasomes, capacitation, and fertilization. The prostate releases more Zn into the seminal plasma during ejaculation, and it plays a significant role in sperm release and motility. During the maternal, labor, perinatal, and neonatal periods, the part of Zn is vital. The average dietary intake of Zn is in the range of 8–12 mg/day in developing countries during the maternal period. Globally, the dietary intake of Zn varies for pregnant and lactating mothers, but the average Zn intake is in the range of 9.6–11.2 mg/day. The absence of Zn and the consequences of this have been discussed using critical evidence. The events and functions of Zn related to successful fertilization have been summarized in detail. Briefly, our current review emphasizes the role of Zn at each stage of human reproduction, from the spermatogenesis process to childbirth. The role of Zn and its supplementation in in vitro fertilization (IVF) opens opportunities for future studies on reproductive biology.

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          Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process.

          Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.
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            The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update.

            Apoptosis is a critically important biological process that plays an essential role in cell fate and homeostasis. An important component of the apoptotic pathway is the family of proteins commonly known as the B cell lymphoma-2 (Bcl-2). The primary role of Bcl-2 family members is the regulation of apoptosis. Although the structure of Bcl-2 family of proteins was reported nearly 10 years ago, however, it still surprises us with its structural and functional complexity and diversity. A number of studies have demonstrated that Bcl-2 family influences many other cellular processes beyond apoptosis which are generally independent of the regulation of apoptosis, suggesting additional roles for Bcl-2. The disruption of the regulation of apoptosis is a causative event in many diseases. Since the Bcl-2 family of proteins is the key regulator of apoptosis, the abnormalities in its function have been implicated in many diseases including cancer, neurodegenerative disorders, ischemia and autoimmune diseases. In the past few years, our understanding of the mechanism of action of Bcl-2 family of proteins and its implications in various pathological conditions has enhanced significantly. The focus of this review is to summarize the current knowledge on the structure and function of Bcl-2 family of proteins in apoptotic cellular processes. A number of drugs have been developed in the past few years that target different Bcl-2 members. The role of Bcl-2 proteins in the pathogenesis of various diseases and their pharmacological significance as effective molecular therapeutic targets is also discussed.
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              Zinc as a Gatekeeper of Immune Function

              After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                22 February 2021
                February 2021
                : 22
                : 4
                : 2188
                Affiliations
                [1 ]Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India; vickramas.16@ 123456gmail.com (S.V.); thanigaivel092@ 123456gmail.com (S.T.)
                [2 ]Unit of Biochemistry, Faculty of Medicine, AIMST University, Semeling, Bedong 08100, Kedah, Malaysia
                [3 ]Department of Biomedical Engineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India; srinivasans@ 123456gmail.com (S.S.); gulothungang@ 123456gmail.com (G.G.); nanmaran3263@ 123456gmail.com (N.R.)
                [4 ]BCX Bioorganics, Krishnasagara Village, Attibele, Bengaluru, Karnataka 562107, India; nancyveenakumari@ 123456gmail.com
                [5 ]Department of Agriculture Engineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India; archanatnau@ 123456gmail.com
                [6 ]Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 602105, India; anbu290785@ 123456gmail.com
                [7 ]Department of Biotechnology, Vel Tech Rangarajan Dr. Sagunthala R&D Institute of Science and Technology, Chennai, Tamil Nadu 600062, India; jeypalanivelu91@ 123456gmail.com
                [8 ]Unit of Psychiatry, Faculty of Medicine, AIMST University, Semeling, Bedong 08100, Malaysia; srikumar@ 123456aimst.edu.my
                Author notes
                [* ]Correspondence: rohini@ 123456aimst.edu.my
                Article
                ijms-22-02188
                10.3390/ijms22042188
                7926410
                33671837
                23f0a840-069b-40f5-84cc-a39eccc5d549
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 January 2021
                : 19 February 2021
                Categories
                Review

                Molecular biology
                zinc,seminal plasma,male infertility,human reproduction,cellular metabolism
                Molecular biology
                zinc, seminal plasma, male infertility, human reproduction, cellular metabolism

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