A Role of the TEX101 Interactome in the Common Aetiology Behind Male Subfertility and Testicular Germ Cell Tumor

Abstract

Patients who develop testicular germ cell tumours (TGCT) are at higher risk to be subfertile than the general population. The conditions are believed to originate during foetal life, however, the mechanisms behind a common aetiology of TGCT and male subfertility remains unknown. Testis-expressed 101 (TEX101) is a glycoprotein that is related to male fertility, and downregulation of the TEX101 gene was shown in pre-diagnostic TGCT patients. In this review, we summarize the current knowledge of TEX101 and its interactome related to fertility and TGCT development. We searched literature and compilation of data from curated databases. There are studies from both human and animals showing that disruption of TEX101 result in abnormal semen parameters and sperm function. Members of the TEX101 interactome, like SPATA19, Ly6k, PICK1, and ODF genes are important for normal sperm function. We found only two studies of TEX101 related to TGCT, however, several genes in its interactome may be associated with TGCT development, such as PLAUR, PRSS21, CD109, and ALP1. Some of the interactome members are related to both fertility and cancer. Of special interest is the presence of the glycosylphosphatidylinositol anchored proteins TEX101 and PRSS21 in basophils that may be coupled to the immune response preventing further development of TGCT precursor cells. The findings of this review indicate that members of the TEX101 interactome could be a part of the link between TGCT and male subfertility.

Testicular Germ Cell Tumor Tissue Biomarker Analysis: A Comparison of Human Protein Atlas and Individual Testicular Germ Cell Tumor Component Immunohistochemistry

“…Again, this is especially relevant in MTGCT and GCNIS, in which the HPA did not separate individual histological components or did not quantify them. Our results confirm the potential of MGMT and, for the first time, show RASSF1 and PRSS21 as tissue biomarkers of normal testicular function whose inactivation is a crucial part of early TGCT tumorigenesis [6,58]. MGMT downregulation has also been shown in patients with azoospermia, solidifying its role as an integral gene for testicular function [68].…”

“…It has been assumed that RASSF1 inactivation may be among the first events of TGCT tumorigenesis [58]. PRSS21 is assumed to act as a tumor suppressor gene whose inactivation plays an essential role in TGCT development [6]. SALL4 is vital in mammalian germ cell development and regulating spermatogonial proliferation [59,60].…”

“…TGCTs have had a rising global incidence of over 70% during the past 20 years, with the highest predicted rise in eastern and southern Europe [3,4]. The reason behind their rising incidence has not been fully understood, but is assumed to be a combination of environmental, inherited and epigenetic factors [5,6]. Their incidence is highest in developed Western countries and among people of European origin (with Norway having the highest incidence world-wide), in which they account for over 60% of all male malignancies between ages 20 and 40 [1,3].…”

Proteomic Landscape of Human Sperm in Patients with Different Spermatogenic Impairments

“…Some of the above-mentioned proteins have previously been found to be associated with infertility. Testis-expressed protein 101 (TEX101) is well-studied glycoprotein and highly related to male fertility (as reviewed in [ 27 ]). Knockout models of TEX101 and its counterpart protein contributes to the maintenance of spermatogenesis and production of fertile sperm [ 28 ].…”

Pre-Diagnostic Circulating RNAs Networks Identify Testicular Germ Cell Tumour Susceptibility Genes

“…In our previous analysis of RNA profiles from the Janus Serum Bank samples using linear models we identified RNAs which were differentially expressed in patients prior to diagnosis of TGCT. These included genes such as TEX101, a male fertility-related gene, and TSIX, X-chromosome inactivation genes (18, 41). As gene products and regulatory elements often operate in close relationships, we used network analysis framework and the tool WGCNA to identify interplay between genes and ncRNAs that could be involved in TGCT development in the years leading up to diagnosis.…”