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Combined evaluation of prolactin-induced peptide (PIP) and extracellular signal-regulated kinase (ERK) as new sperm biomarkers of FSH treatment efficacy in normogonadotropic idiopathic infertile men

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Abstract

Purpose

Nearly, 40% of the causes of male infertility remain idiopathic. The only suggested treatment in idiopathic oligo- and/or asthenozoospermia in normogonadotropic patients is the FSH. In the current clinical practice, efficacy is exclusively assessable through semen analysis after 3 months of treatment. No molecular markers of treatment efficacy are appliable in clinical practice. The aim of the present work is to evaluate the combination of extracellular signal regulated kinase (ERK) 1 and 2 and prolactin inducible peptide (PIP) as potential markers of idiopathic infertility and FSH treatment efficacy.

Methods

Western blot and confocal microscopy were performed to analyze the modulation of PIP and ERK1/2 in idiopathic infertile patients (IIP) sperm cells. Taking advantage of mass spectrometry analysis, we identified these proteins unequivocally in sperm cells.

Results

 We demonstrated a significant decrease of both PIP protein and of ERK1/2 levels in spermatozoa obtained from IIP in comparison to healthy fertile patients (HFP). Conversely, we reported a significant increase of these markers comparing infertile patients before and after 3 months of FSH treatment. Importantly, this correlated with an increase in total number of sperm and sperm motility after FSH treatment. Finally, we identified of PIP and ERK2 proteins in sperm samples by proteomic analysis.

Conclusions

The combined evaluation of ERK1/2 and PIP proteins might represent a useful molecular marker to tailor FSH treatment in the management of male normogonadotropic idiopathic infertility.

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Acknowledgements

We thank Alessia Mahoney, University of Cardiff, Cardiff, United Kingdom for her kind and careful English editing.

Funding

This research received no external funding.

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Author notes

  1. A. Pontecorvi and D. Milardi equally contributed to this work.

Authors and Affiliations

  1. International Scientific Institute Paul VI, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    F. Mancini, F. Di Nicuolo, E. Teveroni, A. Pontecorvi & D. Milardi

  2. Division of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    E. Vergani, C. Bruno, A. Pontecorvi & D. Milardi

  3. Department of Neuroscience, Section of Biophysics, Università Cattolica del Sacro Cuore, Rome, Italy

    G. Bianchetti, G. Maulucci & M. De Spirito

  4. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    G. Bianchetti, G. Maulucci & M. De Spirito

  5. Unit of Andrology and Reproductive Medicine, University Hospital Padua, Padua, Italy

    G. Grande

  6. Department of Laboratory and Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    F. Iavarone & A. Urbani

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  1. F. Mancini
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Contributions

Conceptualization, FM, FDN and DM; methodology, FM, FDN and ET; validation, GB, FI, DM and FM; formal analysis, GB, FI and ET; investigation, FM, FDN; data curation, FM, FI, GG and FDN; writing—original draft preparation, FM, FDN, EV and DM; writing—review and editing, CB, EV, ET and AU; visualization, AP, AU, GM, GG and MDS; supervision, DM, AU and AP. All the authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to F. Mancini.

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The authors declare no conflict of interest.

Research involving human participants and/or animals

The study was carried out following the principles and the guidelines of the Declaration of Helsinki (version 2013) and all subjects gave written.

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Sperm collection and analysis was approved by the Fondazione Policlinico Universitario A. Gemelli, IRCCS, local ethics committee (ID 3943).

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Mancini, F., Di Nicuolo, F., Teveroni, E. et al. Combined evaluation of prolactin-induced peptide (PIP) and extracellular signal-regulated kinase (ERK) as new sperm biomarkers of FSH treatment efficacy in normogonadotropic idiopathic infertile men. J Endocrinol Invest 47, 455–468 (2024). https://doi.org/10.1007/s40618-023-02161-w

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