title: Mammalian target of rapamycin (mTOR): a central regulator of male fertility?
abstract: Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermatogenesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.
authors.affiliation: a Laboratory of Cell Biology, Department of Microscopy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto , Porto , Portugal.|b CICS-UBI - Health Sciences Research Centre, University of Beira Interior , Covilhã , Portugal.
authors.forename: Tito T
authors.initials: TT
authors.lastname: Jesus
authors.affiliation: a Laboratory of Cell Biology, Department of Microscopy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto , Porto , Portugal.|c i3S - Instituto de Investigação e Inovação em Saúde, University of Porto , Porto , Portugal.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Oliveira
authors.affiliation: a Laboratory of Cell Biology, Department of Microscopy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto , Porto , Portugal.|d Centre for Reproductive Genetics Prof. Alberto Barros , Porto , Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Sousa
authors.affiliation: e The Mary M. Wohlford Laboratory for Male Contraceptive Research , Center for Biomedical Research, Population Council , New York , NY , USA.
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: a Laboratory of Cell Biology, Department of Microscopy and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto , Porto , Portugal.|b CICS-UBI - Health Sciences Research Centre, University of Beira Interior , Covilhã , Portugal.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
mesh_terms: D000818:Animals; D005298:Fertility / Q000502:physiology*; D006801:Humans; D008297:Male; D015398:Signal Transduction / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013737:Testis / Q000201:enzymology*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Sertoli cells; fertility; mTOR; male reproduction; spermatogenesis