Vrije Universiteit Brussel

The role of macrophages and mast cells in testicular fibrosis seen in Klinefelter menWillems, Margo

Publication date:2019

Document Version:Other version

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Citation for published version (APA):Willems, M. (2019). The role of macrophages and mast cells in testicular fibrosis seen in Klinefelter men. Postersession presented at Mosa Conference 2019, Maastricht, Netherlands.

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Download date: 19. Jan. 2021

Klinefelter syndrome (KS) affects 1-2 in 1000 newborn males. Mensuffering from this genetic disorder have at least one supplementaryX-chromosome. KS is mostly diagnosed at adult age when consultinga centre for reproductive medicine since 95% of these men areinfertile. During testicular development, a loss of spermatogonialstem cells can be detected. From puberty onwards, testicular fibrosisis detectable. How this germ cell loss and fibrotic process occur,remains unknown.

Introduction

Patient samples: KS, Sertoli cell only (SCO) syndrome, testis atrophyand control testicular tissue from adult, peripubertal and prepubertalpatients

Techniques: Immunohistochemistry, RT-qPCR and RNA sequencing

Genes/proteins included: CD68, tryptase, TNF-α and decorin

Contact details: Margo.Willems@vub.be

This study is the first report revealing an increase in macrophage and mast cell number, as well as an increase in decorin expression in adulttesticular tissue of Klinefelter men. In conclusion, we assume that macrophages and mast cells are not solely responsible for the fibroticprocess in KS. However, these cells and their secretory products definitely play a role in the fibrotic process, leading to infertility. In futureresearch, other possible key players, which will be identified through differential gene-expression analysis, will be studied for their capacity toinitiate testicular fibrosis.

The role of macrophages and mast cells in testicular fibrosis seen in Klinefelter men

Margo Willems, Dorien Van Saen, Ellen GoossensBiology of the Testis; Research Laboratory for Reproduction, Genetics and Regenerative Medicine

Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.

Figure 1: PAS staining in Klinefelter (a and b) and control testicular tissue (c). In someKS, severe fibrosis, hyalinized tubules and Leydig cell hyperplasia can be seen (b),whereas in others, few seminiferous tubules can be detected (a).

The general aim of this study was to characterize the fibroticremodelling in Klinefelter testes through the identification of keyplayers in the initiation of testicular fibrosis. We hypothesized thatmacrophages and/or mast cells and their secretory products wereinvolved in the initiation of the fibrotic process observed in testiculartissue of KS men, since previous research revealed an increase inthese cells in other men with impaired spermatogenesis.

a b

c

a

control

Results

Figure 2: Number of tryptase+ cells (a) and CD68+ cells (b) in adult testicular tissue of KS, SCO and control patients. An increasein both mast cells and macrophages could be detected in the tubular compartment in KS and SCO tissue compared to controls. Asignificant difference of p<0.05 is displayed as (*).

Figure 3: Distribution of decorin in KS testicular tissue after immunohistochemical staining with decorin antibody (a). The tubularwalls are particularly positive for decorin antibody whereas, when seminiferous tubules are degenerated, the distribution is wide-spread all over the sample. Through RT-qPCR, a significant difference in decorin expression was found between KS and control adulttesticular samples, p<0.05, displayed as (*).

Figure 4: Heat map of control samples (left) versus KS samples (right), showing the top 100 genesfor which the adjusted p-value is <0.01 and the absolute log2 fold change >1.

b

KSCTL

a b

Aim of research

Material & Methods

Conclusion