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      Molecular insights into Sertoli cell function: how do metabolic disorders in childhood and adolescence affect spermatogonial fate?

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          Abstract

          Male infertility is a major public health concern globally with unknown etiology in approximately half of cases. The decline in total sperm count over the past four decades and the parallel increase in childhood obesity may suggest an association between these two conditions. Here, we review the molecular mechanisms through which obesity during childhood and adolescence may impair future testicular function. Several mechanisms occurring in obesity can interfere with the delicate metabolic processes taking place at the testicular level during childhood and adolescence, providing the molecular substrate to hypothesize a causal relationship between childhood obesity and the risk of low sperm counts in adulthood.

          Abstract

          Pediatric obesity is increasing worldwide and its contribution to the decline is sperm count has been questioned. By comprehensively reviewing the literature, the authors herein report molecular mechanisms that may suggest the causality of this association.

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          Most cited references154

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            AKT/PKB signaling: navigating downstream.

            The serine/threonine kinase Akt, also known as protein kinase B (PKB), is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Aberrant loss or gain of Akt activation underlies the pathophysiological properties of a variety of complex diseases, including type-2 diabetes and cancer. Here, we review the molecular properties of Akt and the approaches used to characterize its true cellular targets. In addition, we discuss those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration.
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              The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.

              Cell proliferation requires nutrients, energy, and biosynthetic activity to duplicate all macromolecular components during each passage through the cell cycle. It is therefore not surprising that metabolic activities in proliferating cells are fundamentally different from those in nonproliferating cells. This review examines the idea that several core fluxes, including aerobic glycolysis, de novo lipid biosynthesis, and glutamine-dependent anaplerosis, form a stereotyped platform supporting proliferation of diverse cell types. We also consider regulation of these fluxes by cellular mediators of signal transduction and gene expression, including the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR system, hypoxia-inducible factor 1 (HIF-1), and Myc, during physiologic cell proliferation and tumorigenesis.
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                Author and article information

                Contributors
                rossella.cannarella@phd.unict.it
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                3 July 2024
                3 July 2024
                2024
                : 15
                : 5582
                Affiliations
                [1 ]Department of Clinical and Experimental Medicine, University of Catania, ( https://ror.org/03a64bh57) Catania, Italy
                [2 ]GRID grid.239578.2, ISNI 0000 0001 0675 4725, Glickman Urological & Kidney Institute, , Cleveland Clinic Foundation, ; Cleveland, OH USA
                Author information
                http://orcid.org/0000-0003-4599-8487
                http://orcid.org/0009-0003-5395-8140
                http://orcid.org/0000-0002-0127-4295
                Article
                49765
                10.1038/s41467-024-49765-1
                11222552
                38961093
                31bdbb9e-8fca-4ebf-b037-e3ccefb1e904
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 August 2023
                : 12 June 2024
                Categories
                Review Article
                Custom metadata
                © Springer Nature Limited 2024

                Uncategorized
                gonadal disorders,cell signalling
                Uncategorized
                gonadal disorders, cell signalling

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