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Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele

Sperm proteins undergo post-translational modifications, such as phosphorylation, acetylation, and ubiquitination, which in turn play a key role in determining their fertilizing ability. In the current study, we examined the sperm proteome of men with unilateral and bilateral varicocele to identify...

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Autores principales: Panner Selvam, Manesh Kumar, Samanta, Luna, Agarwal, Ashok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246524/
https://www.ncbi.nlm.nih.gov/pubmed/32365753
http://dx.doi.org/10.3390/ijms21093155
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author Panner Selvam, Manesh Kumar
Samanta, Luna
Agarwal, Ashok
author_facet Panner Selvam, Manesh Kumar
Samanta, Luna
Agarwal, Ashok
author_sort Panner Selvam, Manesh Kumar
collection PubMed
description Sperm proteins undergo post-translational modifications, such as phosphorylation, acetylation, and ubiquitination, which in turn play a key role in determining their fertilizing ability. In the current study, we examined the sperm proteome of men with unilateral and bilateral varicocele to identify the key proteins affected by acetylation to gain an insight into the difference in the severity of affected sperm function in the latter. An LTQ-Orbitrap Elite hybrid mass spectrometer system was used to profile the sperm proteome in pooled unilateral and bilateral varicocele patients. Bioinformatics database and tools, such as UniProtKB, Ingenuity Pathway Analysis Software (IPA) and Metacore, were used to identify the differentially expressed proteins (DEPs) involved in the acetylation process. A total of 135 DEPs in the spermatozoa of unilateral and bilateral varicocele patients were found to be affected by acetylation. The majority of these DEPs found were regulated by key transcription factors such as androgen receptor, p53, and NRF2. Furthermore, the DEPs predicted to be affected by the acetylation process were associated with fertilization, acrosome reaction, mitochondrial dysfunction and oxidative stress. Aberrant expression of proteins and their differential acetylation process may affect the normal physiological functions of spermatozoa. Protein–protein interactions identified dysregulation of the proteasome complex in the bilateral varicocele group. Damage to the proteasome complex may result in aggregation of the misfolded proteins, which in turn increase sperm DNA damage and apoptosis in patients with bilateral varicocele.
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spelling pubmed-72465242020-06-11 Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele Panner Selvam, Manesh Kumar Samanta, Luna Agarwal, Ashok Int J Mol Sci Article Sperm proteins undergo post-translational modifications, such as phosphorylation, acetylation, and ubiquitination, which in turn play a key role in determining their fertilizing ability. In the current study, we examined the sperm proteome of men with unilateral and bilateral varicocele to identify the key proteins affected by acetylation to gain an insight into the difference in the severity of affected sperm function in the latter. An LTQ-Orbitrap Elite hybrid mass spectrometer system was used to profile the sperm proteome in pooled unilateral and bilateral varicocele patients. Bioinformatics database and tools, such as UniProtKB, Ingenuity Pathway Analysis Software (IPA) and Metacore, were used to identify the differentially expressed proteins (DEPs) involved in the acetylation process. A total of 135 DEPs in the spermatozoa of unilateral and bilateral varicocele patients were found to be affected by acetylation. The majority of these DEPs found were regulated by key transcription factors such as androgen receptor, p53, and NRF2. Furthermore, the DEPs predicted to be affected by the acetylation process were associated with fertilization, acrosome reaction, mitochondrial dysfunction and oxidative stress. Aberrant expression of proteins and their differential acetylation process may affect the normal physiological functions of spermatozoa. Protein–protein interactions identified dysregulation of the proteasome complex in the bilateral varicocele group. Damage to the proteasome complex may result in aggregation of the misfolded proteins, which in turn increase sperm DNA damage and apoptosis in patients with bilateral varicocele. MDPI 2020-04-30 /pmc/articles/PMC7246524/ /pubmed/32365753 http://dx.doi.org/10.3390/ijms21093155 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Panner Selvam, Manesh Kumar
Samanta, Luna
Agarwal, Ashok
Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele
title Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele
title_full Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele
title_fullStr Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele
title_full_unstemmed Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele
title_short Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele
title_sort functional analysis of differentially expressed acetylated spermatozoal proteins in infertile men with unilateral and bilateral varicocele
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246524/
https://www.ncbi.nlm.nih.gov/pubmed/32365753
http://dx.doi.org/10.3390/ijms21093155
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