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      The Role of Testosterone in Spermatogenesis: Lessons From Proteome Profiling of Human Spermatozoa in Testosterone Deficiency

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          Abstract

          Testosterone is essential to maintain qualitative spermatogenesis. Nonetheless, no studies have been yet performed in humans to analyze the testosterone-mediated expression of sperm proteins and their importance in reproduction. Thus, this study aimed to identify sperm protein alterations in male hypogonadism using proteomic profiling. We have performed a comparative proteomic analysis comparing sperm from fertile controls (a pool of 5 normogonadic normozoospermic fertile men) versus sperm from patients with secondary hypogonadism (a pool of 5 oligozoospermic hypogonadic patients due to isolated LH deficiency). Sperm protein composition was analyzed, after peptide labelling with Isobaric Tags, via liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) on an LTQ Velos-Orbitrap mass spectrometer. LC-MS/MS data were analyzed using Proteome Discoverer. Criteria used to accept protein identification included a false discovery rate (FDR) of 1% and at least 1 peptide match per protein. Up to 986 proteins were identified and, of those, 43 proteins were differentially expressed: 32 proteins were under-expressed and 11 were over-expressed in the pool of hypogonadic patients compared to the controls. Bioinformatic analyses were performed using UniProt Knowledgebase, and the Gene Ontology Consortium database based on PANTHER. Notably, 13 of these 43 differentially expressed proteins have been previously reported to be related to sperm function and spermatogenesis. Western blot analyses for A-Kinase Anchoring Protein 3 (AKAP3) and the Prolactin Inducible Protein (PIP) were used to confirm the proteomics data. In summary, a high-resolution mass spectrometry-based proteomic approach was used for the first time to describe alterations of the sperm proteome in secondary male hypogonadism. Some of the differential sperm proteins described in this study, which include Prosaposin, SMOC-1, SERPINA5, SPANXB1, GSG1, ELSPBP1, fibronectin, 5-oxoprolinase, AKAP3, AKAP4, HYDIN, ROPN1B, ß-Microseminoprotein and Protein S100-A8, could represent new targets for the design of infertility treatments due to androgen deficiency.

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          Proteomics. Tissue-based map of the human proteome.

          Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. Copyright © 2015, American Association for the Advancement of Science.
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            The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences

            The PRoteomics IDEntifications (PRIDE) database ( https://www.ebi.ac.uk/pride/ ) is the world's largest data repository of mass spectrometry-based proteomics data. PRIDE is one of the founding members of the global ProteomeXchange (PX) consortium and an ELIXIR core data resource. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2019. The number of submitted datasets to PRIDE Archive (the archival component of PRIDE) has reached on average around 500 datasets per month during 2021. In addition to continuous improvements in PRIDE Archive data pipelines and infrastructure, the PRIDE Spectra Archive has been developed to provide direct access to the submitted mass spectra using Universal Spectrum Identifiers. As a key point, the file format MAGE-TAB for proteomics has been developed to enable the improvement of sample metadata annotation. Additionally, the resource PRIDE Peptidome provides access to aggregated peptide/protein evidences across PRIDE Archive. Furthermore, we will describe how PRIDE has increased its efforts to reuse and disseminate high-quality proteomics data into other added-value resources such as UniProt, Ensembl and Expression Atlas.
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              Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline

              To update the "Testosterone Therapy in Men With Androgen Deficiency Syndromes" guideline published in 2010.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                19 May 2022
                2022
                : 13
                : 852661
                Affiliations
                [1] 1 Research Group on Human Fertility, International Scientific Institute “Paul VI” , Rome, Italy
                [2] 2 Division of Endocrinology, Fondazione Policlinico Universitario “Agostino Gemelli” Scientific Hospitalization and Treatment Institute (IRCCS) , Rome, Italy
                [3] 3 Department of Biomedical Sciences, Molecular Biology of Reproduction and Development Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Faculty of Medicine and Health Sciences, University of Barcelona , Barcelona, Spain
                [4] 4 Biochemistry and Molecular Genetics Service, Hospital Clínic , Barcelona, Spain
                [5] 5 Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart , Rome, Italy
                Author notes

                Edited by: Aniel Sanchez Puente, Lund University, Sweden

                Reviewed by: Peter Natesan Pushparaj, King Abdulaziz University, Saudi Arabia; Savita Yadav, All India Institute of Medical Sciences, India; Johan Malm, Lund University, Sweden

                *Correspondence: Domenico Milardi, milardid@ 123456yahoo.it

                †Present address: Giuseppe Grande, “San Valentino” Hospital, Regional social and health unit n. 2 (ULSS2) Marca Trevigiana, (TV); Ferran Barrachina, Program in Membrane Biology, Nephrology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States

                ‡These authors have contributed equally to this work and share first authorship

                §These authors have contributed equally to this work and share senior authorship

                This article was submitted to Reproduction, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.852661
                9161277
                35663320
                ae5b5fb6-93af-4cf9-8987-9a77366bae1d
                Copyright © 2022 Grande, Barrachina, Soler-Ventura, Jodar, Mancini, Marana, Chiloiro, Pontecorvi, Oliva and Milardi

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 January 2022
                : 04 April 2022
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 52, Pages: 11, Words: 5947
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                sperm,hypogonadism,proteomics,lh deficiency,testosterone
                Endocrinology & Diabetes
                sperm, hypogonadism, proteomics, lh deficiency, testosterone

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