Age-Related Alterations in the Testicular Proteome of a Non-Human Primate.

Jan B Stöckl,Rüdiger Behr,Georg J Arnold,Nina Schmid,Charis Drummer,Artur Mayerhofer,Thomas Fröhlich,Florian Flenkenthaler

doi:10.3390/cells10061306

Abstract

Aging of human testis and associated cellular changes is difficult to assess. Therefore, we used a translational, non-human primate model to get insights into underlying cellular and biochemical processes. Using proteomics and immunohistochemistry, we analyzed testicular tissue of young (age 2 to 3) and old (age 10 to 12) common marmosets (Callithrix jacchus). Using a mass spectrometry-based proteomics approach, we identified 63,124 peptides, which could be assigned to 5924 proteins. Among them, we found proteins specific for germ cells and somatic cells, such as Leydig and Sertoli cells. Quantitative analysis showed 31 differentially abundant proteins, of which 29 proteins were more abundant in older animals. An increased abundance of anti-proliferative proteins, among them CDKN2A, indicate reduced cell proliferation in old testes. Additionally, an increased abundance of several small leucine rich repeat proteoglycans and other extracellular matrix proteins was observed, which may be related to impaired cell migration and fibrotic events. Furthermore, an increased abundance of proteins with inhibitory roles in smooth muscle cell contraction like CNN1 indicates functional alterations in testicular peritubular cells and may mirror a reduced capacity of these cells to contract in old testes.

Highlights

In many organs, aging is associated with structural alterations and reduced functionality [1,2]
Using a bottom-up mass spectrometry approach, we identified 5924 proteins, among them several specific for germ cells and somatic cells, like Leydig and Sertoli cells, in the testis
To investigate the mechanisms which underly healthy testicular aging in a translational non-human primate model we performed a proteome analysis complemented by immunohistochemistry

Summary

Introduction

In many organs, aging is associated with structural alterations and reduced functionality [1,2]. There is evidence for structural alterations such as enlargement and sclerosis of the peritubular wall [8,9,10] This was disputed by a recent study, which did not find any alterations in the peritubular wall [11]. This study rather reported a reduced spermatogenic efficiency, increased number of proliferating Adark spermatogonia and increased size of Sertoli cell nucleus and nucleolus. Another recent study reported a decline of both Sertoli and Leydig cells in older men and an unchanged steroidogenic capacity of Leydig cells [10]

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