Research ExplorerPublicationsThe Rapamycin-Sensitive Complex of Mammalian Target of Rapam...

The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility

Standard

The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility. / Schell, Christoph; Kretz, Oliver; Liang, Wei; Kiefer, Betina; Schneider, Simon; Sellung, Dominik; Bork, Tillmann; Leiber, Christian; Rüegg, Markus A; Mallidis, Con; Schlatt, Stefan; Mayerhofer, Artur; Huber, Tobias B; Grahammer, Florian.

In: AM J PATHOL, Vol. 186, No. 2, 02.2016, p. 324-36.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schell, C, Kretz, O, Liang, W, Kiefer, B, Schneider, S, Sellung, D, Bork, T, Leiber, C, Rüegg, MA, Mallidis, C, Schlatt, S, Mayerhofer, A, Huber, TB & Grahammer, F 2016, 'The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility', AM J PATHOL, vol. 186, no. 2, pp. 324-36. https://doi.org/10.1016/j.ajpath.2015.10.012

APA

Schell, C., Kretz, O., Liang, W., Kiefer, B., Schneider, S., Sellung, D., Bork, T., Leiber, C., Rüegg, M. A., Mallidis, C., Schlatt, S., Mayerhofer, A., Huber, T. B., & Grahammer, F. (2016). The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility. AM J PATHOL, 186(2), 324-36. https://doi.org/10.1016/j.ajpath.2015.10.012

Vancouver

Schell C, Kretz O, Liang W, Kiefer B, Schneider S, Sellung D et al. The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility. AM J PATHOL. 2016 Feb;186(2):324-36. https://doi.org/10.1016/j.ajpath.2015.10.012

Bibtex

@article{a9d496723c474d7995423ccf98036dc3,
title = "The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility",
abstract = "The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin and its analogs are being increasingly used in solid-organ transplantation. A commonly reported side effect is male subfertility to infertility, yet the precise mechanisms of mTOR interference with male fertility remain obscure. With the use of a conditional mouse genetic approach we demonstrate that deficiency of mTORC1 in the epithelial derivatives of the Wolffian duct is sufficient to cause male infertility. Analysis of spermatozoa from Raptor fl/fl*KspCre mice revealed an overall decreased motility pattern. Both epididymis and seminal vesicles displayed extensive organ regression with increasing age. Histologic and ultrastructural analyses demonstrated increased amounts of destroyed and absorbed spermatozoa in different segments of the epididymis. Mechanistically, genetic and pharmacologic mTORC1 inhibition was associated with an impaired cellular metabolism and a disturbed protein secretion of epididymal epithelial cells. Collectively, our data highlight the role of mTORC1 to preserve the function of the epididymis, ductus deferens, and the seminal vesicles. We thus reveal unexpected new insights into the frequently observed mTORC1 inhibitor side effect of male infertility in transplant recipients.",
keywords = "Animals, Cell Proliferation, Fertility, Male, Mammals, Mice, Transgenic, Multiprotein Complexes, Phosphorylation, Seminal Vesicles, Signal Transduction, Sirolimus, TOR Serine-Threonine Kinases, Transcription Factors, Journal Article, Research Support, Non-U.S. Gov't",
author = "Christoph Schell and Oliver Kretz and Wei Liang and Betina Kiefer and Simon Schneider and Dominik Sellung and Tillmann Bork and Christian Leiber and R{\"u}egg, {Markus A} and Con Mallidis and Stefan Schlatt and Artur Mayerhofer and Huber, {Tobias B} and Florian Grahammer",
note = "Copyright {\textcopyright} 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = feb,
doi = "10.1016/j.ajpath.2015.10.012",
language = "English",
volume = "186",
pages = "324--36",
journal = "AM J PATHOL",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility

AU - Schell, Christoph

AU - Kretz, Oliver

AU - Liang, Wei

AU - Kiefer, Betina

AU - Schneider, Simon

AU - Sellung, Dominik

AU - Bork, Tillmann

AU - Leiber, Christian

AU - Rüegg, Markus A

AU - Mallidis, Con

AU - Schlatt, Stefan

AU - Mayerhofer, Artur

AU - Huber, Tobias B

AU - Grahammer, Florian

N1 - Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2016/2

Y1 - 2016/2

N2 - The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin and its analogs are being increasingly used in solid-organ transplantation. A commonly reported side effect is male subfertility to infertility, yet the precise mechanisms of mTOR interference with male fertility remain obscure. With the use of a conditional mouse genetic approach we demonstrate that deficiency of mTORC1 in the epithelial derivatives of the Wolffian duct is sufficient to cause male infertility. Analysis of spermatozoa from Raptor fl/fl*KspCre mice revealed an overall decreased motility pattern. Both epididymis and seminal vesicles displayed extensive organ regression with increasing age. Histologic and ultrastructural analyses demonstrated increased amounts of destroyed and absorbed spermatozoa in different segments of the epididymis. Mechanistically, genetic and pharmacologic mTORC1 inhibition was associated with an impaired cellular metabolism and a disturbed protein secretion of epididymal epithelial cells. Collectively, our data highlight the role of mTORC1 to preserve the function of the epididymis, ductus deferens, and the seminal vesicles. We thus reveal unexpected new insights into the frequently observed mTORC1 inhibitor side effect of male infertility in transplant recipients.

AB - The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin and its analogs are being increasingly used in solid-organ transplantation. A commonly reported side effect is male subfertility to infertility, yet the precise mechanisms of mTOR interference with male fertility remain obscure. With the use of a conditional mouse genetic approach we demonstrate that deficiency of mTORC1 in the epithelial derivatives of the Wolffian duct is sufficient to cause male infertility. Analysis of spermatozoa from Raptor fl/fl*KspCre mice revealed an overall decreased motility pattern. Both epididymis and seminal vesicles displayed extensive organ regression with increasing age. Histologic and ultrastructural analyses demonstrated increased amounts of destroyed and absorbed spermatozoa in different segments of the epididymis. Mechanistically, genetic and pharmacologic mTORC1 inhibition was associated with an impaired cellular metabolism and a disturbed protein secretion of epididymal epithelial cells. Collectively, our data highlight the role of mTORC1 to preserve the function of the epididymis, ductus deferens, and the seminal vesicles. We thus reveal unexpected new insights into the frequently observed mTORC1 inhibitor side effect of male infertility in transplant recipients.

KW - Animals

KW - Cell Proliferation

KW - Fertility

KW - Male

KW - Mammals

KW - Mice, Transgenic

KW - Multiprotein Complexes

KW - Phosphorylation

KW - Seminal Vesicles

KW - Signal Transduction

KW - Sirolimus

KW - TOR Serine-Threonine Kinases

KW - Transcription Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ajpath.2015.10.012

DO - 10.1016/j.ajpath.2015.10.012

M3 - SCORING: Journal article

C2 - 26683665

VL - 186

SP - 324

EP - 336

JO - AM J PATHOL

JF - AM J PATHOL

SN - 0002-9440

IS - 2

ER -