Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression

A Willems, K De Gendt, J Allemeersch, L B Smith, M Welsh, J V Swinnen, G Verhoeven

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Evidence from several models of hormone depletion and/or replacement and from knockout animals points to a key role of androgens in the control of spermatogenesis. In testes of mice with a Sertoli cell-selective ablation of the androgen receptor (SCARKO), transcriptional profiling, using microarray technology, revealed that, already on postnatal day 10,692 genes are differentially expressed compared with testes of control mice. Further evaluation of a subset of these genes by quantitative RT-PCR suggested that differences in expression may already be evident on day 8 or earlier. As the androgen receptor in mouse Sertoli cells becomes immunologically detectable around day 5, we tried to identify the earliest responses to androgens by a new transcriptional profiling study on testes from 6-day-old SCARKO and control mice. No obvious and novel early androgen response genes, potentially acting as mediators of subsequent indirect androgen actions, could be identified. However, several genes differentially expressed on day 10 already displayed a response to androgen receptor ablation on day 6. Quantitative RT-PCR studies for 12 of these genes on 10 paired SCARKO and control testes from 4-, 6-, 8-, 10-, 20- and 50-day-old mice revealed significant differences in expression level from day 4 onwards for three genes (Eppin, PCI, Cldn11) and from day 6 onwards for one more gene (Rhox5). For at least two of these genes (Rhox5 and Eppin), there is evidence for direct regulation via the androgen receptor. For three additional genes (Gpd1, Tubb3 and Tpd52l1) significantly lower expression in the SCARKO was noted from day 8 onwards. For all the studied genes, an impressive increase in transcript levels was observed between day 4-50 and differential expression was maintained in adulthood. It is concluded that the SCARKO model indicates incipient androgen action in mouse Sertoli cells from day 4 onwards.
Original languageEnglish
Pages (from-to)507-517
Number of pages11
JournalInternational journal of andrology
Volume33
Issue number3
Early online date12 Apr 2009
DOIs
Publication statusPublished - Jun 2010

Fingerprint

Sertoli Cells
Androgen Receptors
Gene Expression
Androgens
Genes
Testis
Polymerase Chain Reaction
Spermatogenesis
Hormones
Technology

Keywords

  • androgens
  • animals
  • crosses, Genetic
  • female
  • gene expression
  • male
  • mice
  • mice, inbred C57BL
  • mice, knockout
  • mice, transgenic
  • receptors, androgen
  • reverse transcriptase polymerase chain reaction
  • sertoli Cells
  • spermatogenesis
  • testis

Cite this

Willems, A., De Gendt, K., Allemeersch, J., Smith, L. B., Welsh, M., Swinnen, J. V., & Verhoeven, G. (2010). Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression. International journal of andrology, 33(3), 507-517. https://doi.org/10.1111/j.1365-2605.2009.00964.x

Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression. / Willems, A; De Gendt, K; Allemeersch, J; Smith, L B; Welsh, M; Swinnen, J V; Verhoeven, G.

In: International journal of andrology, Vol. 33, No. 3, 06.2010, p. 507-517.

Research output: Contribution to journalArticle

Willems, A, De Gendt, K, Allemeersch, J, Smith, LB, Welsh, M, Swinnen, JV & Verhoeven, G 2010, 'Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression', International journal of andrology, vol. 33, no. 3, pp. 507-517. https://doi.org/10.1111/j.1365-2605.2009.00964.x
Willems, A ; De Gendt, K ; Allemeersch, J ; Smith, L B ; Welsh, M ; Swinnen, J V ; Verhoeven, G. / Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression. In: International journal of andrology. 2010 ; Vol. 33, No. 3. pp. 507-517.
@article{dc4f804519674ed29a8879a36fd200e2,
title = "Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression",
abstract = "Evidence from several models of hormone depletion and/or replacement and from knockout animals points to a key role of androgens in the control of spermatogenesis. In testes of mice with a Sertoli cell-selective ablation of the androgen receptor (SCARKO), transcriptional profiling, using microarray technology, revealed that, already on postnatal day 10,692 genes are differentially expressed compared with testes of control mice. Further evaluation of a subset of these genes by quantitative RT-PCR suggested that differences in expression may already be evident on day 8 or earlier. As the androgen receptor in mouse Sertoli cells becomes immunologically detectable around day 5, we tried to identify the earliest responses to androgens by a new transcriptional profiling study on testes from 6-day-old SCARKO and control mice. No obvious and novel early androgen response genes, potentially acting as mediators of subsequent indirect androgen actions, could be identified. However, several genes differentially expressed on day 10 already displayed a response to androgen receptor ablation on day 6. Quantitative RT-PCR studies for 12 of these genes on 10 paired SCARKO and control testes from 4-, 6-, 8-, 10-, 20- and 50-day-old mice revealed significant differences in expression level from day 4 onwards for three genes (Eppin, PCI, Cldn11) and from day 6 onwards for one more gene (Rhox5). For at least two of these genes (Rhox5 and Eppin), there is evidence for direct regulation via the androgen receptor. For three additional genes (Gpd1, Tubb3 and Tpd52l1) significantly lower expression in the SCARKO was noted from day 8 onwards. For all the studied genes, an impressive increase in transcript levels was observed between day 4-50 and differential expression was maintained in adulthood. It is concluded that the SCARKO model indicates incipient androgen action in mouse Sertoli cells from day 4 onwards.",
keywords = "androgens, animals, crosses, Genetic, female, gene expression, male, mice, mice, inbred C57BL, mice, knockout, mice, transgenic, receptors, androgen, reverse transcriptase polymerase chain reaction, sertoli Cells, spermatogenesis, testis",
author = "A Willems and {De Gendt}, K and J Allemeersch and Smith, {L B} and M Welsh and Swinnen, {J V} and G Verhoeven",
year = "2010",
month = "6",
doi = "10.1111/j.1365-2605.2009.00964.x",
language = "English",
volume = "33",
pages = "507--517",
journal = "International journal of andrology",
issn = "0105-6263",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression

AU - Willems, A

AU - De Gendt, K

AU - Allemeersch, J

AU - Smith, L B

AU - Welsh, M

AU - Swinnen, J V

AU - Verhoeven, G

PY - 2010/6

Y1 - 2010/6

N2 - Evidence from several models of hormone depletion and/or replacement and from knockout animals points to a key role of androgens in the control of spermatogenesis. In testes of mice with a Sertoli cell-selective ablation of the androgen receptor (SCARKO), transcriptional profiling, using microarray technology, revealed that, already on postnatal day 10,692 genes are differentially expressed compared with testes of control mice. Further evaluation of a subset of these genes by quantitative RT-PCR suggested that differences in expression may already be evident on day 8 or earlier. As the androgen receptor in mouse Sertoli cells becomes immunologically detectable around day 5, we tried to identify the earliest responses to androgens by a new transcriptional profiling study on testes from 6-day-old SCARKO and control mice. No obvious and novel early androgen response genes, potentially acting as mediators of subsequent indirect androgen actions, could be identified. However, several genes differentially expressed on day 10 already displayed a response to androgen receptor ablation on day 6. Quantitative RT-PCR studies for 12 of these genes on 10 paired SCARKO and control testes from 4-, 6-, 8-, 10-, 20- and 50-day-old mice revealed significant differences in expression level from day 4 onwards for three genes (Eppin, PCI, Cldn11) and from day 6 onwards for one more gene (Rhox5). For at least two of these genes (Rhox5 and Eppin), there is evidence for direct regulation via the androgen receptor. For three additional genes (Gpd1, Tubb3 and Tpd52l1) significantly lower expression in the SCARKO was noted from day 8 onwards. For all the studied genes, an impressive increase in transcript levels was observed between day 4-50 and differential expression was maintained in adulthood. It is concluded that the SCARKO model indicates incipient androgen action in mouse Sertoli cells from day 4 onwards.

AB - Evidence from several models of hormone depletion and/or replacement and from knockout animals points to a key role of androgens in the control of spermatogenesis. In testes of mice with a Sertoli cell-selective ablation of the androgen receptor (SCARKO), transcriptional profiling, using microarray technology, revealed that, already on postnatal day 10,692 genes are differentially expressed compared with testes of control mice. Further evaluation of a subset of these genes by quantitative RT-PCR suggested that differences in expression may already be evident on day 8 or earlier. As the androgen receptor in mouse Sertoli cells becomes immunologically detectable around day 5, we tried to identify the earliest responses to androgens by a new transcriptional profiling study on testes from 6-day-old SCARKO and control mice. No obvious and novel early androgen response genes, potentially acting as mediators of subsequent indirect androgen actions, could be identified. However, several genes differentially expressed on day 10 already displayed a response to androgen receptor ablation on day 6. Quantitative RT-PCR studies for 12 of these genes on 10 paired SCARKO and control testes from 4-, 6-, 8-, 10-, 20- and 50-day-old mice revealed significant differences in expression level from day 4 onwards for three genes (Eppin, PCI, Cldn11) and from day 6 onwards for one more gene (Rhox5). For at least two of these genes (Rhox5 and Eppin), there is evidence for direct regulation via the androgen receptor. For three additional genes (Gpd1, Tubb3 and Tpd52l1) significantly lower expression in the SCARKO was noted from day 8 onwards. For all the studied genes, an impressive increase in transcript levels was observed between day 4-50 and differential expression was maintained in adulthood. It is concluded that the SCARKO model indicates incipient androgen action in mouse Sertoli cells from day 4 onwards.

KW - androgens

KW - animals

KW - crosses, Genetic

KW - female

KW - gene expression

KW - male

KW - mice

KW - mice, inbred C57BL

KW - mice, knockout

KW - mice, transgenic

KW - receptors, androgen

KW - reverse transcriptase polymerase chain reaction

KW - sertoli Cells

KW - spermatogenesis

KW - testis

U2 - 10.1111/j.1365-2605.2009.00964.x

DO - 10.1111/j.1365-2605.2009.00964.x

M3 - Article

VL - 33

SP - 507

EP - 517

JO - International journal of andrology

JF - International journal of andrology

SN - 0105-6263

IS - 3

ER -