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Alterations in the proliferative/apoptotic equilibrium in semen of adolescents with varicocele

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

Abstract

Purpose

To verify if the presence of varicocele (grades II and III) with and without seminal alterations, using the 5th centile cutoff values in table A1.1 of the World Health Organization (WHO, 2010) manual, alters the seminal plasma levels of proteins DNASE1 (deoxyribonuclease-1) and IGFBP7 (Insulin-like growth factor-binding protein 7), which are related to apoptosis regulation and cell proliferation, respectively, demonstrating that these proteins are important for correct spermatogenesis.

Methods

This cross sectional study was performed at the Sao Paulo Federal University Paulo between May 2014 and April 2016. A total of 61 male adolescents were included in this study, of which 20 controls without varicocele (C), 22 with varicocele and normal semen analysis (VNS) and 19 with varicocele and altered semen analysis (VAS). Seminal plasma from each patient was used for Western blotting analysis of individual protein levels. Values of each protein were normalized to a testicular housekeeping protein (PARK7—protein deglycase DJ-1).

Results

Levels of IGFBP7 protein are increased in varicocele. Levels of DNASE1 are progressively decreased in varicocele (lower in varicocele and normal semen analysis, lowest in varicocele and altered semen analysis) when compared to adolescents without varicocele. DNASE1 levels are positively correlated with sperm concentration and morphology (correlation values of 0.400 and 0.404, respectively; p values of 0.001 and 0.001, respectively).

Conclusion

In conclusion, in adolescents, seminal plasma levels of IGFBP7, responsible for proliferative activity, are increased in varicocele grades II and III, and DNASE1, responsible for apoptosis regulation, are lower in varicocele, lowest in varicocele and low semen quality. These proteins demonstrate molecular alterations brought upon by varicocele. Moreover, DNASE1 is capable of discriminating a varicocele that causes alterations to semen quality from one that does not. We propose that the initial response of varicocele is to increase proliferative activity which, if followed by regulation of apoptosis, may lead to the ejaculation of a population of sperm that are in accordance with WHO cutoff values but, in the presence of dysregulated apoptosis, leads to lower sperm concentration and morphology.

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Authors and Affiliations

  1. Department of Surgery, Division of Urology, Universidade Federal de São Paulo, R Embau, 231, 04039-060, Sao Paulo, SP, Brazil

    Larissa Berloffa Belardin, Paula Toni Del Giudice, Mariana Camargo, Paula Intasqui, Mariana Pereira Antoniassi, Ricardo Pimenta Bertolla & Agnaldo Pereira Cedenho

  2. Hospital São Paulo, São Paulo, Brazil

    Ricardo Pimenta Bertolla

Authors
  1. Larissa Berloffa Belardin
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  2. Paula Toni Del Giudice
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  3. Mariana Camargo
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  4. Paula Intasqui
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  5. Mariana Pereira Antoniassi
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  6. Ricardo Pimenta Bertolla
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  7. Agnaldo Pereira Cedenho
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Corresponding author

Correspondence to Ricardo Pimenta Bertolla.

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Conflicts of interest

None declared.

Authors’ roles

L.B.B. was responsible for conception and design of the study, acquisition of samples for analysis, acquisition of confirmatory proteomics data, interpretation of data, drafting of the article, revision of the article, and final approval for submission. P.T.D.G. participated in the acquisition of samples for analysis, interpretation of data, revision of the article, and final approval for submission. M.C. participated in the acquisition of samples for analysis, interpretation of data, revision of the article and final approval for submission. P.I. participated in the interpretation of data, revision of the article, and final approval for submission. M.P.A. participated in the interpretation of data, revision of the article, and final approval for submission. R.P.B. participated in conception and design of the study, analysis and interpretation of data, drafting of the article, and final approval for submission. A.P.C. participated in the conception and design of the study, clinical discussion of all the patients included in the study, discussion of results, drafting of the article, and final approval for submission.

Funding

L.B.B. was a recipient of a Masters scholarship from the Sao Paulo Research Foundation - FAPESP (process number 2014/11636-6). A.P.C. and R.P.B. are recipients of a Scientific Productivity scholarship from the Brazilian National Council for Scientific and Technological Development – CNPq (processes numbers 313077/2014-2 and 306616/2013-0, respectively). This work was supported by a Research Grant from the Sao Paulo Research Foundation – FAPESP (process number 2014/17185-6) and from the Brazilian National Council for Scientific and Technological Development (process number 454514/2014-0).

Ethical approval

Institutional Review Board approval was obtained from the Sao Paulo Federal University Research Ethics Committee (CAAE: 31701614.4.0000.5505).

Additional information

Capsule

In adolescents, seminal plasma levels of IGFBP7 are higher in varicocele, and of DNASE1 are lower in varicocele, lowest in varicocele in the presence of low semen quality.

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Belardin, L.B., Del Giudice, P.T., Camargo, M. et al. Alterations in the proliferative/apoptotic equilibrium in semen of adolescents with varicocele. J Assist Reprod Genet 33, 1657–1664 (2016). https://doi.org/10.1007/s10815-016-0808-z

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  • DOI: https://doi.org/10.1007/s10815-016-0808-z

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