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Total urokinase-type plasminogen activator (uPA) levels in seminal plasma are associated with positive assisted reproductive technology outcomes

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The plasminogen/plasmin system is an important extracellular protease system whose function has been implicated in male reproductive function. However, its clinical relevance to fertility in human assisted reproduction technologies has not been systematically investigated. Here, we examined whether total and active populations of urokinase-type plasminogen activator (uPA) in human seminal plasma and spermatozoa are predictive of pregnancy outcome in couples undergoing insemination or intracytoplasmic sperm injection (ICSI).

Methods

Seminal samples from 182 men, 5 donors, 21 patients attending the clinic for infertility screening, and 156 for assisted reproduction technology (ART) treatment (insemination and ICSI), were evaluated. Total uPA in seminal plasma and spermatozoa as well as active uPA in seminal plasma were measured by ELISA. Sperm quality parameters and fertility outcomes following insemination or ICSI were correlated with the uPA values.

Results

Active uPA in seminal plasma was positively correlated to the volume of the ejaculate, total number of spermatozoa in the ejaculate, and total motility. However, these values were not prognostic of fertility outcomes. Total uPA in spermatozoa was inversely related to sperm concentration, total sperm in ejaculate, morphology, and total and progressive motility, and this measure was not related to fertility. Importantly, however, higher values of total uPA in seminal plasma were detected in cases that resulted in pregnancy compared to those that did not follow insemination and ICSI treatment.

Conclusions

Taken together, these findings lay the foundation for further understanding the mechanism by which total uPA in seminal plasma affects fertility and how this marker can be used as a predictor of ART outcomes.

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Acknowledgements

The authors are grateful to Prof. Bill Holt (University of Sheffield) and Prof. Francesca Duncan (Northwestern University) for their critical reviews of the manuscript and English improvement.

Funding

The study was funded by the Centre for Development of Industrial Technology (CDTI, Spanish Ministry of Economy, Industry and Competitiveness) with FEDER funds (IDI-20120531) and 20040/GERM/16 from Fundación Séneca de la Región de Murcia.

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Authors and Affiliations

  1. IVI Murcia, 30008, Murcia, Spain

    Juan Carlos Martinez-Soto, José Landeras, Marta Mollá, María Nicolás, Laura Fernández-Olmedilla & Martina Trabalón

  2. Institute for Biomedical Research of Murcia IMIB-Arrixaca, Murcia, Spain

    Juan Carlos Martinez-Soto, José Landeras, Marta Mollá, Irene Mondejar, Pilar Coy & Joaquín Gadea

  3. Department of Physiology, International Excellence Campus for Higher Education and Research (Campus Mare Nostrum), University of Murcia, 30100, Murcia, Spain

    Irene Mondejar, Pilar Coy & Joaquín Gadea

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  1. Juan Carlos Martinez-Soto
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  2. José Landeras
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  4. Irene Mondejar
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  6. Laura Fernández-Olmedilla
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  7. Martina Trabalón
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  8. Pilar Coy
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  9. Joaquín Gadea
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Corresponding author

Correspondence to Joaquín Gadea.

Ethics declarations

This study was conducted with institutional approval from Instituto Valenciano de Infertilidad (Ref. 1210-MU-109JM). Couples undergoing assisted reproduction treatment in Instituto Valenciano de Infertilidad (IVI-Murcia, Spain) and sperm donors were included after signing the informed consent.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Preliminary results have been presented to 31st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), Lisbon (Portugal), June 14–17, 2015 and 33rd European Society of Human Reproduction and Embryology Annual Meeting, Geneva (Switzerland), July2–5, 2017.

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Martinez-Soto, J.C., Landeras, J., Mollá, M. et al. Total urokinase-type plasminogen activator (uPA) levels in seminal plasma are associated with positive assisted reproductive technology outcomes. J Assist Reprod Genet 35, 1091–1101 (2018). https://doi.org/10.1007/s10815-018-1164-y

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  • DOI: https://doi.org/10.1007/s10815-018-1164-y

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