Proteomic Analysis Reveals that Topoisomerase 2A is Associated with Defective Sperm Head Morphology

Abstract

Male infertility is widespread and estimated to affect 1 in 20 men. Although in some cases the etiology of the condition is well understood, for at least 50% of men, the underlying cause is yet to be classified. Male infertility, or subfertility, is often diagnosed by looking at total sperm produced, motility of the cells and overall morphology. Although counting spermatozoa and their associated motility is routine, morphology assessment is highly subjective, mainly because of the procedure being based on microscopic examination. A failure to diagnose male-infertility or sub-fertility has led to a situation where assisted conception is often used unnecessarily. As such, biomarkers of male infertility are needed to help establish a more consistent diagnosis. In the present study, we compared nuclear extracts from both high- and low-quality spermatozoa by LC-MS/MS based proteomic analysis. Our data shows that nuclear retention of specific proteins is a common facet among low-quality sperm cells. We demonstrate that the presence of Topoisomerase 2A in the sperm head is highly correlated to poor head morphology. Topoisomerase 2A is therefore a potential new biomarker for confirming male infertility in clinical practice.

Comparison of RNA content from hydrophobic interaction chromatography‐isolated seminal plasma exosomes from intrauterine insemination (IUI) pregnancies

“…Only a few studies have measured protein levels of low-quality spermatozoa (predictive of poor IVF outcomes) in comparison to high-quality spermatozoa, those finding many different proteins significantly more abundant in either of the groups (Netherton et al, 2018(Netherton et al, ,2020. Our study includes semen from samples used in IUI;…”

Implementing a preimplantation proteomic approach to advance assisted reproduction technologies in the framework of predictive, preventive, and personalized medicine

“…Netherton et al analyzed nuclear extracts of human semen comparing high-and low-quality semen using LC-MS/MS and found that nuclear retention of specific proteins is a common facet among low-quality sperm cells. In particular, it was found that the presence of the enzyme topoisomerase 2A (TOP2A) in the sperm head is highly correlated to poor head morphology, and as a result, it could serve as a potential biomarker for confirming male infertility in clinical practice [62]. Vigodner et al researched the occurrence of the post-translational modification, sumoylation, in normal and abnormal sperm samples.…”

Case Report: Balanced Reciprocal Translocation t (17; 22) (p11.2; q11.2) and 10q23.31 Microduplication in an Infertile Male Patient Suffering From Teratozoospermia

“…An interaction network was established according to the genes at the chromosome breakpoints in our patient (Figure 4). Interestingly, the genes for kinesin family member 20B (KIF20B), DNA topoisomerase III-alpha (TOP3A), LLGL scribble cell polarity complex component 1 (LLGL1), phosphoribosyl pyrophosphate synthetaseassociated protein 2 (PRPSAP2), and cell division cycle 45 (CDC45) were closely associated with DNA topoisomerase II alpha (TOP2A) expression, which has been found to be associated with the defective morphology of sperm heads (Netherton et al, 2020). As found in our patient, the shape of the sperm head is the most common morphological abnormality reported.…”