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      Mammalian Sperm Fertility Related Proteins

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          Abstract

          Infertility is an important aspect of human and animal reproduction and still presents with much etiological ambiguity. As fifty percent of infertility is related to the male partner, molecular investigations on sperm and seminal plasma can lead to new knowledge on male infertility. Several comparisons between fertile and infertile human and other species sperm proteome have shown the existence of potential fertility markers. These proteins have been categorized into energy related, structural and other functional proteins which play a major role in sperm motility, capacitation and sperm-oocyte binding. The data from these studies show the impact of sperm proteome studies on identifying different valuable markers for fertility screening. In this article, we review recent development in unraveling sperm fertility related proteins.

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          Control of hyperactivation in sperm.

          Susan S Suarez (2008)
          Sperm hyperactivation is critical to fertilization, because it is required for penetration of the zona pellucida. Hyperactivation may also facilitate release of sperm from the oviductal storage reservoir and may propel sperm through mucus in the oviductal lumen and the matrix of the cumulus oophorus. Hyperactivation is characterized by high amplitude, asymmetrical flagellar bending. This is a review of the original literature on the mechanisms that regulate hyperactivation, including physiological factors and signaling pathways. Computer-assisted semen analysis systems can be used to identify hyperactivated sperm by setting minimum thresholds for curvilinear velocity (VSL) and lateral head movement and a maximum threshold for path linearity. Hyperactivation is triggered by a rise in flagellar Ca(2+) resulting from influx primarily through plasma membrane CatSper channels and possibly also by release of Ca(2+) from a store in the redundant nuclear envelope. It requires increased pH and ATP production. The physiological signals that trigger the rise in Ca(2+) remain elusive, but there is evidence that the increased Ca(2+) acts through a calmodulin/calmodulin kinase pathway. Hyperactivation is considered part of the capacitation process; however, the regulatory pathway that triggers hyperactivation can operate independently from that which prepares sperm to undergo the acrosome reaction. Hyperactivation may be modulated by chemotactic signals to turn sperm toward the oocyte. Little is known about exactly what triggers hyperactivation in human sperm. This information could enable clinicians to develop reliable fertility assays to assess normal hyperactivation in human sperm samples.
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            The Sept4 septin locus is required for sperm terminal differentiation in mice.

            Hermann Steller, Katia Manova-Todorova, Holger Kissel … (2005)
            The murine septin4 gene (Sept4) has been implicated in diverse cellular functions, including cytokinesis, apoptosis, and tumor suppression. Here, we investigated the function of Sept4 proteins during mouse development by creating a targeted deletion of the Sept4 genomic locus. Sept4 mutant mice are viable but male sterile due to immotile and structurally defective sperm. During spermatogenesis, Sept4 proteins were essential for proper mitochondrial architecture and establishment of the annulus, a ring-like structure in the tail region of sperm. In addition, Sept4 mutant sperm showed defects in the elimination of residual cytoplasm during sperm maturation and had increased staining for the caspase inhibitor XIAP. This is consistent with a role of the proapoptotic Sept4 protein ARTS in promoting caspase-mediated removal of cytoplasm via inhibition of XIAP. Our results indicate that Sept4 proteins play distinct but evolutionarily conserved functions in different cellular compartments.
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              Epigenetics, spermatogenesis and male infertility.

              Singh Rajender, Kelsey Avery, Ashok Agarwal (2015)
              Epigenetic modifications characterized by DNA methylation, histone modifications, and chromatin remodeling are important regulators in a number of biological processes, including spermatogenesis. Several genes in the testes are regulated through epigenetic mechanisms, indicating a direct influence of epigenetic mechanisms on the process of spermatogenesis. In the present article, we have provided a comprehensive review of the epigenetic processes in the testes, correlation of epigenetic aberrations with male infertility, impact of environmental factors on the epigenome and male fertility, and significance of epigenetic changes/aberrations in assisted reproduction. The literature review suggested a significant impact of epigenetic aberrations (epimutations) on spermatogenesis, and this could lead to male infertility. Epimutations (often hypermethylation) in several genes, namely MTHFR, PAX8, NTF3, SFN, HRAS, JHM2DA, IGF2, H19, RASGRF1, GTL2, PLAG1, D1RAS3, MEST, KCNQ1, LIT1, and SNRPN, have been reported in association with poor semen parameters or male infertility. Environmental toxins/drugs may affect fertility via epigenetic modifications. For example, 5-aza-2'-deoxycytidine, an anticancer agent, causes a decrease in global DNA methylation that leads to altered sperm morphology, decreased sperm motility, decreased fertilization capacity, and decreased embryo survival. Similarly, Endocrine disruptors, such as methoxychlor (an estrogenic pesticide) and vinclozolin (an anti-androgenic fungicide) have been found by experiments on animals to affect epigenetic modifications that may cause spermatogenic defects in subsequent generations. Assisted reproduction procedures that have been considered rather safe, are now being implicated in inducing epigenetic changes that could affect fertility in subsequent generations. Techniques such as intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI) may increase the incidence of imprinting disorders and adversely affect embryonic development by using immature spermatozoa that may not have established proper imprints or global methylation. Epigenetic changes, in contrast to genetic aberrations, may be less deleterious because they are potentially reversible. Further research could identify certain drugs capable of reversing epigenetic changes. Copyright © 2011 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Med Sci
                Journal ID (iso-abbrev): Int J Med Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Medical Sciences
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1449-1907
                Publication date Collection: 2013
                Publication date (Electronic): 23 September 2013
                Volume: 10
                Issue: 12
                Pages: 1649-1657
                Affiliations
                1. School of Biosciences and Biotechnology, Faculty of Science and Technology, University Kebangsaan Malaysia, Selangor, Malaysia;
                2. Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
                Author notes
                ✉ Corresponding author: Sheila Nathan, DPhil. School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor DE, Malaysia. Tel: +603-89213862 Fax: +603-89252698 Email: sheila@ 123456ukm.my .

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: ijmsv10p1649
                DOI: 10.7150/ijms.6395
                PMC ID: 3804790
                PubMed ID: 24151436
                SO-VID: 4f281d63-b145-4112-aff5-2b3eb62d3f85
                Copyright © © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                History
                Date received : 3 April 2013
                Date accepted : 23 July 2013
                Categories
                Subject: Review

                ScienceOpen disciplines: Medicine
                Keywords: proteomics,sperm,fertility,protein,infertility.
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: proteomics, sperm, fertility, protein, infertility.

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