Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis

William W Wright, Liam Smith, Candace Kerr, Martin Charron

Research output: Contribution to journalArticle

Abstract

The finding of large, stage-specific changes in secretion of procathepsin L by rat Sertoli cells has led to the hypothesis that this proenzyme promotes the survival, replication, or differentiation of spermatogenic cells. Experiments described herein used a mouse model to test this hypothesis. To prove that mice are appropriate for this purpose, we first demonstrate that mature mouse Sertoli cells express cathepsin L mRNA in the same stage-specific manner as rat Sertoli cells and they also secrete procathepsin L. To test whether catalytically active cathepsin L is required for normal spermatogenesis, we examined the testes of 110- to 120-day-old furless mice, which express catalytically inactive cathepsin L. Morphologic examination of testes of furless mice revealed both normal and atrophic seminiferous tubules. Enumeration of atrophic tubules in furless and control mice demonstrates that lack of functional cathepsin L results in a 12-fold increase in seminiferous tubule atrophy. To determine whether lack of functional cathepsin L affects the production of male germ cells in apparently normal, nonatrophic tubules, we compared numbers in control and furless mice of preleptotene spermatocytes, pachytene spermatocytes, and round spermatids per Sertoli cell. Results demonstrate that the lack of functional cathepsin L causes a 16% reduction in formation of preleptotene spermatocytes and a 25% reduction in differentiation of these cells into pachytene spermatocyte. These results suggest that procathepsin L either directly or indirectly has two distinct functions in the testis. This proenzyme prevents atrophy of seminiferous tubules and promotes the formation of preleptotene spermatocytes and the differentiation of these meiotic cells into pachytene spermatocytes.

Original languageEnglish (US)
Pages (from-to)680-687
Number of pages8
JournalBiology of Reproduction
Volume68
Issue number2
DOIs
StatePublished - Feb 1 2003

Fingerprint

Cathepsin L
Spermatogenesis
Spermatocytes
Sertoli Cells
Seminiferous Tubules
Testis
Cell Differentiation
Enzyme Precursors
Atrophy
Spermatids
Germ Cells
Messenger RNA

Keywords

  • Gamete biology
  • Sertoli cells
  • Spermatid
  • Spermatogenesis
  • Testis

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis. / Wright, William W; Smith, Liam; Kerr, Candace; Charron, Martin.

In: Biology of Reproduction, Vol. 68, No. 2, 01.02.2003, p. 680-687.

Research output: Contribution to journalArticle

Wright, William W ; Smith, Liam ; Kerr, Candace ; Charron, Martin. / Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis. In: Biology of Reproduction. 2003 ; Vol. 68, No. 2. pp. 680-687.
@article{0ecd573bb0d643049e4fd1c6985ed254,
title = "Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis",
abstract = "The finding of large, stage-specific changes in secretion of procathepsin L by rat Sertoli cells has led to the hypothesis that this proenzyme promotes the survival, replication, or differentiation of spermatogenic cells. Experiments described herein used a mouse model to test this hypothesis. To prove that mice are appropriate for this purpose, we first demonstrate that mature mouse Sertoli cells express cathepsin L mRNA in the same stage-specific manner as rat Sertoli cells and they also secrete procathepsin L. To test whether catalytically active cathepsin L is required for normal spermatogenesis, we examined the testes of 110- to 120-day-old furless mice, which express catalytically inactive cathepsin L. Morphologic examination of testes of furless mice revealed both normal and atrophic seminiferous tubules. Enumeration of atrophic tubules in furless and control mice demonstrates that lack of functional cathepsin L results in a 12-fold increase in seminiferous tubule atrophy. To determine whether lack of functional cathepsin L affects the production of male germ cells in apparently normal, nonatrophic tubules, we compared numbers in control and furless mice of preleptotene spermatocytes, pachytene spermatocytes, and round spermatids per Sertoli cell. Results demonstrate that the lack of functional cathepsin L causes a 16{\%} reduction in formation of preleptotene spermatocytes and a 25{\%} reduction in differentiation of these cells into pachytene spermatocyte. These results suggest that procathepsin L either directly or indirectly has two distinct functions in the testis. This proenzyme prevents atrophy of seminiferous tubules and promotes the formation of preleptotene spermatocytes and the differentiation of these meiotic cells into pachytene spermatocytes.",
keywords = "Gamete biology, Sertoli cells, Spermatid, Spermatogenesis, Testis",
author = "Wright, {William W} and Liam Smith and Candace Kerr and Martin Charron",
year = "2003",
month = "2",
day = "1",
doi = "10.1095/biolreprod.102.006726",
language = "English (US)",
volume = "68",
pages = "680--687",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "2",

}

TY - JOUR

T1 - Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis

AU - Wright, William W

AU - Smith, Liam

AU - Kerr, Candace

AU - Charron, Martin

PY - 2003/2/1

Y1 - 2003/2/1

N2 - The finding of large, stage-specific changes in secretion of procathepsin L by rat Sertoli cells has led to the hypothesis that this proenzyme promotes the survival, replication, or differentiation of spermatogenic cells. Experiments described herein used a mouse model to test this hypothesis. To prove that mice are appropriate for this purpose, we first demonstrate that mature mouse Sertoli cells express cathepsin L mRNA in the same stage-specific manner as rat Sertoli cells and they also secrete procathepsin L. To test whether catalytically active cathepsin L is required for normal spermatogenesis, we examined the testes of 110- to 120-day-old furless mice, which express catalytically inactive cathepsin L. Morphologic examination of testes of furless mice revealed both normal and atrophic seminiferous tubules. Enumeration of atrophic tubules in furless and control mice demonstrates that lack of functional cathepsin L results in a 12-fold increase in seminiferous tubule atrophy. To determine whether lack of functional cathepsin L affects the production of male germ cells in apparently normal, nonatrophic tubules, we compared numbers in control and furless mice of preleptotene spermatocytes, pachytene spermatocytes, and round spermatids per Sertoli cell. Results demonstrate that the lack of functional cathepsin L causes a 16% reduction in formation of preleptotene spermatocytes and a 25% reduction in differentiation of these cells into pachytene spermatocyte. These results suggest that procathepsin L either directly or indirectly has two distinct functions in the testis. This proenzyme prevents atrophy of seminiferous tubules and promotes the formation of preleptotene spermatocytes and the differentiation of these meiotic cells into pachytene spermatocytes.

AB - The finding of large, stage-specific changes in secretion of procathepsin L by rat Sertoli cells has led to the hypothesis that this proenzyme promotes the survival, replication, or differentiation of spermatogenic cells. Experiments described herein used a mouse model to test this hypothesis. To prove that mice are appropriate for this purpose, we first demonstrate that mature mouse Sertoli cells express cathepsin L mRNA in the same stage-specific manner as rat Sertoli cells and they also secrete procathepsin L. To test whether catalytically active cathepsin L is required for normal spermatogenesis, we examined the testes of 110- to 120-day-old furless mice, which express catalytically inactive cathepsin L. Morphologic examination of testes of furless mice revealed both normal and atrophic seminiferous tubules. Enumeration of atrophic tubules in furless and control mice demonstrates that lack of functional cathepsin L results in a 12-fold increase in seminiferous tubule atrophy. To determine whether lack of functional cathepsin L affects the production of male germ cells in apparently normal, nonatrophic tubules, we compared numbers in control and furless mice of preleptotene spermatocytes, pachytene spermatocytes, and round spermatids per Sertoli cell. Results demonstrate that the lack of functional cathepsin L causes a 16% reduction in formation of preleptotene spermatocytes and a 25% reduction in differentiation of these cells into pachytene spermatocyte. These results suggest that procathepsin L either directly or indirectly has two distinct functions in the testis. This proenzyme prevents atrophy of seminiferous tubules and promotes the formation of preleptotene spermatocytes and the differentiation of these meiotic cells into pachytene spermatocytes.

KW - Gamete biology

KW - Sertoli cells

KW - Spermatid

KW - Spermatogenesis

KW - Testis

UR - http://www.scopus.com/inward/record.url?scp=0037307043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037307043&partnerID=8YFLogxK

U2 - 10.1095/biolreprod.102.006726

DO - 10.1095/biolreprod.102.006726

M3 - Article

C2 - 12533435

AN - SCOPUS:0037307043

VL - 68

SP - 680

EP - 687

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 2

ER -