Altered ureido protein modification profiles in seminal plasma extracellular vesicles of non-normozoospermic men

Front Endocrinol (Lausanne). 2023 Mar 22:14:1113824. doi: 10.3389/fendo.2023.1113824. eCollection 2023.

Abstract

Introduction: Extracellular vesicles (EVs) have been recognized as key players in numerous physiological functions. These vesicles alter their compositions attuned to the health and disease states of the organism. In men, significant changes in the proteomic composition(s) of seminal plasma EVs (sEVs) have already been found to be related to infertility.

Methods: Methods: In this study, we analyze the posttranslational configuration of sEV proteomes from normozoospermic (NZ) men and non-normozoospermic (non-NZ) men diagnosed with teratozoospermia and/or asthenozoospermia by unbiased, discovery-driven proteomics and advanced bioinformatics, specifically focusing on citrulline (Cit) and homocitrulline (hCit) posttranscriptional residues, both considered product of ureido protein modifications.

Results and discussion: Significant increase in the proteome-wide cumulative presence of hCit together with downregulation of Cit in specific proteins related to decisive molecular functions have been encountered in sEVs of non-NZ subjects. These findings identify novel culprits with a higher chance of affecting fundamental aspects of sperm functional quality and define potential specific diagnostic and prognostic non-invasive markers for male infertility.

Keywords: carbamylation; citrullination; citrulline; deimination; exosomes; homocitrulline; seminal plasma; ureido protein modifications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Extracellular Vesicles*
  • Humans
  • Infertility, Male* / diagnosis
  • Infertility, Male* / metabolism
  • Male
  • Proteomics / methods
  • Semen / metabolism
  • Spermatozoa / metabolism

Grants and funding

This work was funded by the National Institute of Health: Instituto de Salud Carlos III-ISCIII, Spain (PI22/00443) and (CP21/00096), grants co-funded by the European Union. This work was also funded by the Ministry of Science and Innovation, Spain (PID2020-114885RB-C21) and (RYC2021- 030946-I), grants co-funded by the European Union. Support for this work was provided by the Research and Education Council of the Comunidad de Madrid-CAM, Spain (2018-T1/BIO-10633) and the Intensification Project for Research in Health 2022 – ‘Projecte Intensificació Recerca en Salut’ (PIRS2022-PP10697) awarded by Diputació de Lleida, Spain. This work has also been co-financed by the Ministry of Science and Innovation, Spain, with funds from the European Union NextGenerationEU (PRTR-C17.I1) and the Autonomous Community of Catalonia within the framework of the 2023 Biotechnology Plan Applied to Health (EVBRAINTARGET-Y7340-ACPPCCOL007), coordinated by the Institute for Bioengineering of Catalonia (IBEC). AS acknowledges a Ramón y Cajal program tenure track contract (RYC2021-030946-I), awarded on the 2022 call by the National Research Council-Agencia Estatal de Investigación-AEI, Spain, co-funded by the European Union. XG-P acknowledges a Miguel Servet program tenure track contract (CP21/00096) of the ISCIII, awarded on the 2021 call under the Health Strategy Action, co-funded by the European Union. CL PhD is funded by the Regional Ministry of Science, Universities, and Innovation of the CAM and the European Social Fund for the recruitment of predoctoral researchers (PEJD-2019-PRE/BIO- 16475). MM PhD is funded by the 2022 FPI fellowship (PR2021-097934) of the Ministry of Science and Innovation, Spain. JASM PhD is funded by the 2022 fellowship “Ajuts al Talent en Investigació Biomèdica” awarded by Diputació de Lleida, Spain. IRBLLEIDA, JASM, and XG-P are co-funded by CERCA Program/Generalitat de Catalunya.