Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development

Ariane Willems, Sergio R Batlouni, Arantza Esnal, Johannes V Swinnen, Philippa T K Saunders, Richard M Sharpe, Luiz R França, Karel De Gendt, Guido Verhoeven

Research output: Contribution to journalArticle

62 Citations (Scopus)
3 Downloads (Pure)

Abstract

The observation that mice with a selective ablation of the androgen receptor (AR) in Sertoli cells (SC) (SCARKO mice) display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli) and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin). Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2). It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.
Original languageEnglish
Article numbere14168
Number of pages16
JournalPloS ONE
Volume5
Issue number11
DOIs
Publication statusPublished - 30 Nov 2010

Fingerprint

Sertoli Cells
Sertoli cells
Androgen Receptors
Ablation
Genes
mice
Cells
Lanthanum
Functional analysis
Cell adhesion
Vimentin
Permeation
Androgens
Polarization
Germ Cells
germ cells
androgen receptors
mouse AR protein
lanthanum
genes

Keywords

  • animals
  • cadherins
  • cell differentiation
  • cytoskeleton
  • female
  • gene expression
  • immunohistochemistry
  • male
  • membrane proteins
  • mice
  • mice, inbred C57BL
  • mice, knockout
  • microscopy, electron
  • nerve tissue proteins
  • phosphoproteins
  • receptors, androgen
  • reverse transcriptase polymerase chain reaction
  • sertoli cells
  • spermatogenesis
  • testis
  • time factors
  • vimentin

Cite this

Willems, A., Batlouni, S. R., Esnal, A., Swinnen, J. V., Saunders, P. T. K., Sharpe, R. M., ... Verhoeven, G. (2010). Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development. PloS ONE, 5(11), [e14168]. https://doi.org/10.1371/journal.pone.0014168

Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development. / Willems, Ariane; Batlouni, Sergio R; Esnal, Arantza; Swinnen, Johannes V; Saunders, Philippa T K; Sharpe, Richard M; França, Luiz R; De Gendt, Karel; Verhoeven, Guido.

In: PloS ONE, Vol. 5, No. 11, e14168, 30.11.2010.

Research output: Contribution to journalArticle

Willems, A, Batlouni, SR, Esnal, A, Swinnen, JV, Saunders, PTK, Sharpe, RM, França, LR, De Gendt, K & Verhoeven, G 2010, 'Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development', PloS ONE, vol. 5, no. 11, e14168. https://doi.org/10.1371/journal.pone.0014168
Willems, Ariane ; Batlouni, Sergio R ; Esnal, Arantza ; Swinnen, Johannes V ; Saunders, Philippa T K ; Sharpe, Richard M ; França, Luiz R ; De Gendt, Karel ; Verhoeven, Guido. / Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development. In: PloS ONE. 2010 ; Vol. 5, No. 11.
@article{88421b3978ea48579a3bee0b79eb1131,
title = "Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development",
abstract = "The observation that mice with a selective ablation of the androgen receptor (AR) in Sertoli cells (SC) (SCARKO mice) display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli) and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin). Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2). It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.",
keywords = "animals, cadherins, cell differentiation, cytoskeleton, female, gene expression, immunohistochemistry, male, membrane proteins, mice, mice, inbred C57BL, mice, knockout, microscopy, electron, nerve tissue proteins, phosphoproteins, receptors, androgen, reverse transcriptase polymerase chain reaction, sertoli cells, spermatogenesis, testis, time factors, vimentin",
author = "Ariane Willems and Batlouni, {Sergio R} and Arantza Esnal and Swinnen, {Johannes V} and Saunders, {Philippa T K} and Sharpe, {Richard M} and Fran{\cc}a, {Luiz R} and {De Gendt}, Karel and Guido Verhoeven",
year = "2010",
month = "11",
day = "30",
doi = "10.1371/journal.pone.0014168",
language = "English",
volume = "5",
journal = "PloS ONE",
issn = "1932-6203",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "11",

}

TY - JOUR

T1 - Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development

AU - Willems, Ariane

AU - Batlouni, Sergio R

AU - Esnal, Arantza

AU - Swinnen, Johannes V

AU - Saunders, Philippa T K

AU - Sharpe, Richard M

AU - França, Luiz R

AU - De Gendt, Karel

AU - Verhoeven, Guido

PY - 2010/11/30

Y1 - 2010/11/30

N2 - The observation that mice with a selective ablation of the androgen receptor (AR) in Sertoli cells (SC) (SCARKO mice) display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli) and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin). Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2). It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

AB - The observation that mice with a selective ablation of the androgen receptor (AR) in Sertoli cells (SC) (SCARKO mice) display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli) and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin). Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2). It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

KW - animals

KW - cadherins

KW - cell differentiation

KW - cytoskeleton

KW - female

KW - gene expression

KW - immunohistochemistry

KW - male

KW - membrane proteins

KW - mice

KW - mice, inbred C57BL

KW - mice, knockout

KW - microscopy, electron

KW - nerve tissue proteins

KW - phosphoproteins

KW - receptors, androgen

KW - reverse transcriptase polymerase chain reaction

KW - sertoli cells

KW - spermatogenesis

KW - testis

KW - time factors

KW - vimentin

U2 - 10.1371/journal.pone.0014168

DO - 10.1371/journal.pone.0014168

M3 - Article

C2 - 21152390

VL - 5

JO - PloS ONE

JF - PloS ONE

SN - 1932-6203

IS - 11

M1 - e14168

ER -