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A young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging

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Curley, Michael ; Milne, Laura ; Smith, Sarah ; Jørgensen, Anne ; Frederiksen, Hanne ; Hadoke, Patrick ; Potter, Paul ; Smith, Lee B. / A young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging. I: FASEB Journal. 2019 ; Bind 33, Nr. 1. s. 978-995.

Bibtex

@article{d048059fa1004f13bdd388b5740a31d5,
title = "A young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging",
abstract = "Testicular Leydig cells (LCs) are the primary source of circulating androgen in men. As men age, circulating androgen levels decline. However, whether reduced LC steroidogenesis results from specific effects of aging within LCs or reflects degenerative alterations to the wider supporting microenvironment is unclear; inability to separate intrinsic LC aging from that of the testicular microenvironment in vivo has made this question difficult to address. To resolve this, we generated novel mouse models of premature aging, driven by CDGSH iron sulfur domain 2 ( Cisd2) deletion, to separate the effects of cell intrinsic aging from extrinsic effects of aging on LC function. At 6 mo of age, constitutive Cisd2-deficient mice display signs of premature aging, including testicular atrophy, reduced LC and Sertoli cell (SC) number, decreased circulating testosterone, increased luteinizing hormone/testosterone ratio, and decreased expression of steroidogenic mRNAs, appropriately modeling primary testicular dysfunction observed in aging men. However, mice with Cisd2 deletion (and thus premature aging) restricted to either LCs or SCs were protected against testicular degeneration, demonstrating that age-related LCs dysfunction cannot be explained by intrinsic aging within either the LC or SC lineages alone. We conclude that age-related LC dysfunction is largely driven by aging of the supporting testicular microenvironment.-Curley, M., Milne, L., Smith, S., J{\o}rgensen, A., Frederiksen, H., Hadoke, P., Potter, P., Smith, L. B. A Young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging.",
keywords = "Gonadotropin, Steroidogenesis, Testis, Testosterone, Autophagy-Related Proteins, Testis/physiology, Male, Aging, Premature, Mice, Knockout, Animals, Carrier Proteins/genetics, Gene Deletion, Nerve Tissue Proteins/genetics, Models, Animal, Mice, Luteinizing Hormone/blood, Leydig Cells/physiology, Testosterone/blood",
author = "Michael Curley and Laura Milne and Sarah Smith and Anne J{\o}rgensen and Hanne Frederiksen and Patrick Hadoke and Paul Potter and Smith, {Lee B}",
year = "2019",
doi = "10.1096/fj.201800612R",
language = "English",
volume = "33",
pages = "978--995",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "Federation of American Societies for Experimental Biology",
number = "1",

}

RIS

TY - JOUR

T1 - A young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging

AU - Curley, Michael

AU - Milne, Laura

AU - Smith, Sarah

AU - Jørgensen, Anne

AU - Frederiksen, Hanne

AU - Hadoke, Patrick

AU - Potter, Paul

AU - Smith, Lee B

PY - 2019

Y1 - 2019

N2 - Testicular Leydig cells (LCs) are the primary source of circulating androgen in men. As men age, circulating androgen levels decline. However, whether reduced LC steroidogenesis results from specific effects of aging within LCs or reflects degenerative alterations to the wider supporting microenvironment is unclear; inability to separate intrinsic LC aging from that of the testicular microenvironment in vivo has made this question difficult to address. To resolve this, we generated novel mouse models of premature aging, driven by CDGSH iron sulfur domain 2 ( Cisd2) deletion, to separate the effects of cell intrinsic aging from extrinsic effects of aging on LC function. At 6 mo of age, constitutive Cisd2-deficient mice display signs of premature aging, including testicular atrophy, reduced LC and Sertoli cell (SC) number, decreased circulating testosterone, increased luteinizing hormone/testosterone ratio, and decreased expression of steroidogenic mRNAs, appropriately modeling primary testicular dysfunction observed in aging men. However, mice with Cisd2 deletion (and thus premature aging) restricted to either LCs or SCs were protected against testicular degeneration, demonstrating that age-related LCs dysfunction cannot be explained by intrinsic aging within either the LC or SC lineages alone. We conclude that age-related LC dysfunction is largely driven by aging of the supporting testicular microenvironment.-Curley, M., Milne, L., Smith, S., Jørgensen, A., Frederiksen, H., Hadoke, P., Potter, P., Smith, L. B. A Young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging.

AB - Testicular Leydig cells (LCs) are the primary source of circulating androgen in men. As men age, circulating androgen levels decline. However, whether reduced LC steroidogenesis results from specific effects of aging within LCs or reflects degenerative alterations to the wider supporting microenvironment is unclear; inability to separate intrinsic LC aging from that of the testicular microenvironment in vivo has made this question difficult to address. To resolve this, we generated novel mouse models of premature aging, driven by CDGSH iron sulfur domain 2 ( Cisd2) deletion, to separate the effects of cell intrinsic aging from extrinsic effects of aging on LC function. At 6 mo of age, constitutive Cisd2-deficient mice display signs of premature aging, including testicular atrophy, reduced LC and Sertoli cell (SC) number, decreased circulating testosterone, increased luteinizing hormone/testosterone ratio, and decreased expression of steroidogenic mRNAs, appropriately modeling primary testicular dysfunction observed in aging men. However, mice with Cisd2 deletion (and thus premature aging) restricted to either LCs or SCs were protected against testicular degeneration, demonstrating that age-related LCs dysfunction cannot be explained by intrinsic aging within either the LC or SC lineages alone. We conclude that age-related LC dysfunction is largely driven by aging of the supporting testicular microenvironment.-Curley, M., Milne, L., Smith, S., Jørgensen, A., Frederiksen, H., Hadoke, P., Potter, P., Smith, L. B. A Young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging.

KW - Gonadotropin

KW - Steroidogenesis

KW - Testis

KW - Testosterone

KW - Autophagy-Related Proteins

KW - Testis/physiology

KW - Male

KW - Aging, Premature

KW - Mice, Knockout

KW - Animals

KW - Carrier Proteins/genetics

KW - Gene Deletion

KW - Nerve Tissue Proteins/genetics

KW - Models, Animal

KW - Mice

KW - Luteinizing Hormone/blood

KW - Leydig Cells/physiology

KW - Testosterone/blood

UR - http://www.scopus.com/inward/record.url?scp=85059244299&partnerID=8YFLogxK

U2 - 10.1096/fj.201800612R

DO - 10.1096/fj.201800612R

M3 - Journal article

C2 - 30080443

VL - 33

SP - 978

EP - 995

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 1

ER -

ID: 55123908