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      Sugar‐coated sperm: Unraveling the functions of the mammalian sperm glycocalyx

      review-article
      1 , 1 ,
      Molecular Reproduction and Development
      John Wiley and Sons Inc.

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          SUMMARY

          Mammalian spermatozoa are coated with a thick glycocalyx that is assembled during sperm development, maturation, and upon contact with seminal fluid. The sperm glycocalyx is critical for sperm survival in the female reproductive tract and is modified during capacitation. The complex interplay among the various glycoconjugates generates numerous signaling motifs that may regulate sperm function and, as a result, fertility. Nascent spermatozoa assemble their own glycans while the cells still possess a functional endoplasmic reticulum and Golgi in the seminiferous tubule, but once spermatogenesis is complete, they lose the capacity to produce glycoconjugates de novo. Sperm glycans continue to be modified, during epididymal transit by extracellular glycosidases and glycosyltransferases. Furthermore, epididymal cells secrete glycoconjugates (glycophosphatidylinositol‐anchored glycoproteins and glycolipids) and glycan‐rich microvesicles that can fuse with the maturing sperm membrane. The sperm glycocalyx mediates numerous functions in the female reproductive tract, including the following: inhibition of premature capacitation; passage through the cervical mucus; protection from innate and adaptive female immunity; formation of the sperm reservoir; and masking sperm proteins involved in fertilization. The immense diversity in sperm‐associated glycans within and between species forms a remarkable challenge to our understanding of essential sperm glycan functions. Mol. Reprod. Dev. 82: 635–650, 2015. © 2015 The Authors. Molecular Reproduction and Development published by Wiley Periodicals, Inc.

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          A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets.

          Understanding mammalian spermatozoan development and the events surrounding fertilization has grown slowly, in part because of uncertainty about the number and identity of the cellular components involved. Determination of those transcripts expressed specifically by germ cells should provide an inclusive list of probable critical proteins. Here, total mouse testis transcript profiles were trimmed of transcripts found in cultures enriched in Sertoli or interstitial cells to yield a germ cell-enriched transcript profile. Monitoring of changes of this profile in the developing testis identified 1,652 genes whose transcript abundance increased markedly coincident with the onset of meiosis. Remarkably, 351 of these genes (approximately equal to 20%) appear to be expressed only in the male germline. Germ cell-specific transcripts are much less common earlier in testis development. Further analysis of the UniGene EST database coupled with quantitative PCR indicates that approximately 4% of the mouse genome is dedicated to expression in postmeiotic male germ cells. Most or many of the protein products of these transcripts are probably retained in mature spermatozoa. Targeted disruption of 19 of these genes has indicated that a majority have roles critical for normal fertility. Thus, we find an astonishing number of genes expressed specifically by male germ cells late in development. This extensive group provides a plethora of potential targets for germ cell-directed contraception and a staggering number of candidate proteins that could be critical for fertilization.
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            The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily.

            Tumor cell-derived collagenase stimulatory factor, renamed extracellular matrix metalloproteinase inducer (EMMPRIN), is a M(r) approximately 58,000 glycoprotein which is located on the outer surface of human tumor cells and which interacts with fibroblasts to stimulate expression of several matrix metalloproteinases in the fibroblasts. In this study, we have used several approaches to isolate a complementary DNA encoding EMMPRIN. Several peptide sequences obtained from the isolated M(r) 58,000 glycoprotein are found in the translated complementary DNA clone, verifying its identity. Computer database searches indicate that EMMPRIN is a member of the immunoglobulin superfamily and that the deduced amino acid sequence of EMMPRIN is identical to that recently reported for human basigin and M6 antigen, molecules of previously undetermined biological function.
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              Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution.

              Humans are genetically deficient in the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc) because of an Alu-mediated inactivating mutation of the gene encoding the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase (CMAH). This mutation occurred after our last common ancestor with bonobos and chimpanzees, and before the origin of present-day humans. Here, we take multiple approaches to estimate the timing of this mutation in relationship to human evolutionary history. First, we have developed a method to extract and identify sialic acids from bones and bony fossils. Two Neanderthal fossils studied had clearly detectable Neu5Ac but no Neu5Gc, indicating that the CMAH mutation predated the common ancestor of humans and the Neanderthal, approximately 0.5-0.6 million years ago (mya). Second, we date the insertion event of the inactivating human-specific sahAluY element that replaced the ancestral AluSq element found adjacent to exon 6 of the CMAH gene in the chimpanzee genome. Assuming Alu source genes based on a phylogenetic tree of human-specific Alu elements, we estimate the sahAluY insertion time at approximately 2.7 mya. Third, we apply molecular clock analysis to chimpanzee and other great ape CMAH genes and the corresponding human pseudogene to estimate an inactivation time of approximately 2.8 mya. Taken together, these studies indicate that the CMAH gene was inactivated shortly before the time when brain expansion began in humankind's ancestry, approximately 2.1-2.2 mya. In this regard, it is of interest that although Neu5Gc is the major sialic acid in most organs of the chimpanzee, its expression is selectively down-regulated in the brain, for as yet unknown reasons.
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                Author and article information

                Journal
                Mol Reprod Dev
                Mol. Reprod. Dev
                10.1002/(ISSN)1098-2795
                MRD
                Molecular Reproduction and Development
                John Wiley and Sons Inc. (Hoboken )
                1040-452X
                1098-2795
                09 June 2015
                September 2015
                : 82
                : 9 ( doiID: 10.1002/mrd.v82.9 )
                : 635-650
                Affiliations
                [ 1 ] Division of Comparative Pathology and Medicine Department of Pathology Glycobiology Research and Training CenterUniversity of California San Diego La Jolla California
                Author notes
                [*] [* ] Corresponding author:

                Division of Comparative Pathology and Medicine, Department of Pathology, Glycobiology Research and Training Center, University of California San Diego, Biomedical Research Facility 2, Room 4124, 9500 Gilman Drive 0687, La Jolla, CA 92093‐0687. E‐mail: pgagneux@ 123456ucsd.edu

                Article
                MRD22500
                10.1002/mrd.22500
                4744710
                26061344
                eeedcc0b-be2d-47e0-b885-42c72240cf2e
                © 2015 The Authors. Molecular Reproduction and Development published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 14 December 2014
                : 30 April 2015
                Page count
                Pages: 16
                Funding
                Funded by: NIHGMS Grant
                Award ID: #1065732
                Funded by: UCSD
                Award ID: Core A P01HL107150
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                mrd22500
                September 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.6 mode:remove_FC converted:03.02.2016

                Developmental biology
                Developmental biology

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