Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 12/2016

01-12-2016 | Gamete Biology

An association between sperm PLCζ levels and varicocele?

Authors: Elham Janghorban-Laricheh, Nasim Ghazavi-Khorasgani, Marziyeh Tavalaee, Dina Zohrabi, Homayon Abbasi, Mohammad H. Nasr- Esfahani

Published in: Journal of Assisted Reproduction and Genetics | Issue 12/2016

Login to get access

Abstract

Purpose

We aimed to compare the expression of phospholipase C ζ (PLCζ), as one of the main sperm factors involved in oocyte activation, at both RNA and protein levels in fertile men and those with varicocele.

Methods

This study included 35 individuals with male factor infertility presenting primary infertility with grade II and III unilateral varicocele and 20 fertile men without varicocele. Semen parameters were assessed according to WHO 2010. Sperm DNA fragmentation, relative expression of PLCζ at messenger RNA, and protein levels were evaluated by sperm chromatin structure assay (SCSA), real-time PCR, and Western blot analysis, respectively.

Results

The results of this study reveal that the mean relative expression of PLCζ was significantly lower in individuals with varicocele compared to fertile men at both transcription and translation levels. In addition, the percentage of DNA fragmentation was significantly higher in infertile men with varicocele compared to fertile men.

Conclusions

The findings of the present study illustrate that one of the etiologies of reduced fertility associated with varicocele is the low expression of PLCζ. This effect could subsequently reduce the sperm ability to induce oocyte activation. Therefore, these results hold promise to modify our understanding of reproductive physiology of varicocele state.
Literature
1.
Kantartzi PD, Goulis CD, Goulis GD, Papadimas I. Male infertility and varicocele: myths and reality. Hippokratia. 2007;11(3):99–104.PubMedPubMedCentral
2.
Homade A, Esteves S, Agawal A. Varicocele and male infertility: current concepts, controversies and consensus. Springer brief in reproductive biology. Springer; 2016. ISBN: 978-3-319-24934-6.
3.
Agarwal A, Deepinder F, Cocuzza M, Agarwal R, Short RA, Sabanegh E, et al. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology. 2007;70(3):532–8.CrossRefPubMed
4.
5.
Amdani SN, Yeste M, Jones C, Coward K. Sperm factors and oocyte activation: current controversies and considerations. Biol Reprod. 2015;93(2):50.CrossRefPubMed
6.
Anifandis G, Messini CI, Dafopoulos K, Daponte A, Messinis IE. Sperm contributions to oocyte activation: more that meets the eye. J Assist Reprod Genet. 2016;33(3):313–6.CrossRefPubMed
7.
8.
9.
Kashir J, Nomikos M, Swann K, Lai FA. PLCζ or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis. Mol Hum Reprod. 2015;21(5):383–8.CrossRefPubMed
10.
11.
Satouh Y, Nozawa K, Ikawa M. Sperm postacrosomal WW domain-binding protein is not required for mouse egg activation. Biol Reprod. 2015;93(4):94.CrossRefPubMed
12.
Aghajanpour S, Ghaedi K, Salamian A, Deemeh MR, Tavalaee M, Moshtaghian J. Quantitative expression of phospholipase C zeta, as an index to assess fertilization potential of a semen sample. Hum Reprod. 2011;26(11):2950–6.CrossRefPubMed
13.
Yelumalai S, Yeste M, Jones C, Amdani SN, Kashir J, Mounce G, et al. Total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta are significantly correlated with fertilization rates after intracytoplasmic sperm injection. Fertil Steril. 2015;104(3):561–8.e4.CrossRefPubMed
14.
Kashir J, Jones C, Lee HC, Rietdorf K, Nikiforaki D, Durrans C, et al. Loss of activity mutations in phospholipase C zeta (PLCζ) abolishes calcium oscillatory ability of human recombinant protein in mouse oocytes. Hum Reprod. 2011;26(12):3372–87.CrossRefPubMedPubMedCentral
15.
Kashir J, Konstantinidis M, Jones C, Lemmon B, Lee HC, Hamer R, et al. A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility. Hum Reprod. 2012;27(1):222–31.CrossRefPubMed
16.
Kashir J, Konstantinidis M, Jones C, Heindryckx B, De Sutter P, Parrington J, et al. Characterization of two heterozygous mutations of the oocyte activation factor phospholipase C zeta (PLCζ) from an infertile man by use of minisequencing of individual sperm and expression in somatic cells. Fertil Steril. 2012;98(2):423–31.CrossRefPubMed
17.
Kashir J, Jones C, Mounce G, Ramadan WM, Lemmon B, Heindryckx B, et al. Variance in total levels of phospholipase C zeta (PLC-ζ) in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of oocyte activation capability. Fertil Steril. 2013;99(1):107–17.CrossRefPubMed
18.
Heytens E, Parrington J, Coward K, Young C, Lambrecht S, Yoon SY, et al. Reduced amounts and abnormal forms of phospholipase C zeta (PLCzeta) in spermatozoa from infertile men. Hum Reprod. 2009;24(10):2417–28.CrossRefPubMed
19.
Knott JG, Kurokawa M, Fissore RA, Schultz RM, Williams CJ. Transgenic RNA interference reveals role for mouse sperm phospholipase Czeta in triggering Ca2+ oscillations during fertilization. Biol Reprod. 2005;72(4):992–6.CrossRefPubMed
20.
Tavalaee M, Nasr-Esfahani MH. Expression profile of PLCf, PAWP, and TR-KIT in association with fertilization potential, embryo development, and pregnancy outcomes in globozoospermic candidates for intra-cytoplasmic sperm injection and artificial oocyte activation. Andrology. 2016; 1–7.
21.
Kashir J, Heynen A, Jones C, Durrans C, Craig J, Gadea J, et al. Effects of cryopreservation and density-gradient washing on phospholipase C zeta concentrations in human spermatozoa. Reprod Biomed Online. 2011;23(2):263–7.CrossRefPubMed
22.
Sanusi R, Yu Y, Nomikos M, Lai FA, Swann K. Rescue of failed oocyte activation after ICSI in a mouse model of male factor infertility by recombinant phospholipase Cζ. Mol Hum Reprod. 2015;21(10):783–91.CrossRefPubMedPubMedCentral
23.
World Health Organization. Examination and processing human semen. 5th ed. Cambridge: Cambridge University Press; 2010.
24.
25.
Shiraishi K, Takihara H, Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis. World J Urol. 2010;28(3):359–64.CrossRefPubMed
26.
Shiraishi K, Matsuyama H, Takihara H. Pathophysiology of varicocele in male infertility in the era of assisted reproductive technology. Int J Urol. 2012;19(6):538–50.CrossRefPubMed
27.
Bahreinian M, Tavalaee M, Abbasi H, Kiani-Esfahani A, Shiravi AH, Nasr-Esfahani MH. DNA hypomethylation predisposes sperm to DNA damage in individuals with varicocele. Syst Biol Reprod Med. 2015;61(4):179–86.CrossRefPubMed
28.
Naughton CK, Nangia AK, Agarwal A. Pathophysiology of varicoceles in male infertility. Hum Reprod Update. 2001;7(5):473–81.CrossRefPubMed
29.
Setchell BP. The Parkes lecture. Heat and the testis. J Reprod Fertil. 1998;114(2):179–94. Review.CrossRefPubMed
30.
Durairajanayagam D, Agarwal A, Ong C. Causes, effects and molecular mechanisms of testicular heat stress. Reprod Biomed Online. 2015;30(1):14–27.CrossRefPubMed
31.
Afiyani AA, Deemeh MR, Tavalaee M, Razi M, Bahadorani M, Shokrollahi B, et al. Evaluation of heat-shock protein A2 (HSPA2) in male rats before and after varicocele induction. Mol Reprod Dev. 2014;81(8):766–76.PubMed
32.
Gadea J, Molla M, Selles E, Marco MA, Garcia-Vazquez FA, Gardon JC. Reduced glutathione content in human sperm is decreased after cryopreservation: effect of to the addition of reduced glutathione the freezing and thawing extenders. Cryobiology. 2011;62(1):40–6.CrossRefPubMed
33.
Grasa P, Coward K, Young C, Parrington J. The pattern of localization of the putative oocyte activation factor, phospholipase Czeta, in uncapacitated, capacitated, and ionophore-treated human spermatozoa. Hum Reprod. 2008;23(11):2513–22.CrossRefPubMed
34.
Young C, Grasa P, Coward K, Davis LC, Parrington J. Phospholipase C zeta undergoes dynamic changes in its pattern of localization in sperm during capacitation and the acrosome reaction. Fertil Steril. 2009;91(5):2230–42.CrossRefPubMed
35.
Oliveira A, Neto A, Almeida C, Silva-Ramos M, Versos R, Barros A, et al. Comparative study of gene expression in patients with varicocele by microarray technology. Andrologia. 2012;44:260–5.CrossRefPubMed
36.
Kimmins S, Kotaja N, Davidson I, Sassone-Corsi P. Testis-specific transcription mechanisms promoting male germ-cell differentiation. Reproduction. 2004;128(1):5–12.CrossRefPubMed
37.
Cui J, Holmes EH, Greene TG, Liu PK. Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain. FASEB J. 2000;14(7):955–67.PubMedPubMedCentral
38.
Simon L, Proutski I, Stevenson M, Jennings D, McManus J, Lutton D, et al. Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod Biomed Online. 2013;26(1):68–78.CrossRefPubMed
39.
Simon L, Liu L, Murphy K, Ge S, Hotaling J, Aston KI, et al. Comparative analysis of three sperm DNA damage assays and sperm nuclear protein content in couples undergoing assisted reproduction treatment. Hum Reprod. 2014;29(5):904–17.CrossRefPubMed
40.
Anifandis G, Bounartzi T, Messini CI, Dafopoulos K, Markandona R, Sotiriou S, et al. Sperm DNA fragmentation measured by Halosperm does not impact on embryo quality and ongoing pregnancy rates in IVF/ICSI treatments. Andrologia. 2015;47(3):295–302.CrossRefPubMed
41.
42.
Nasr-Esfahani MH, Abasi H, Razavi S, Ashrafi S, Tavalaee M. Varicocelectomy: semen parameters and protamine deficiency. Int J Androl. 2009;32(2):115–22.CrossRefPubMed
43.
Li F, Yamaguchi K, Okada K, Matsushita K, Ando M, Chiba K, et al. Significant improvement of sperm DNA quality after microsurgical repair of varicocele. Syst Biol Reprod Med. 2012;58(5):274–7.CrossRefPubMed
44.
Tavalaee M, Bahreinian M, Barekat F, Abbasi H, Nasr-Esfahani MH. Effect of varicocelectomy on sperm functional characteristics and DNA methylation. Andrologia. 2015;47(8):904–9.PubMed
45.
Park JH, Kim SK, Kim J, Kim JH, Chang JH, Jee BC. Relationship between phospholipase C zeta immunoreactivity and DNA fragmentation and oxidation in human sperm. Obstet Gynecol Sci. 2015;58(3):232–8.CrossRefPubMedPubMedCentral
46.
Pasqualotto FF, Braga DP, Figueira RC, Setti AS, Iaconelli Jr A, Borges Jr E. Varicocelectomy does not impact pregnancy outcomes following intracytoplasmic sperm injection procedures. J Androl. 2012;33(2):239–43.CrossRefPubMed
47.
Pathak P, Chandrashekar A, Hakky TS, Pastuszak AW. Varicocele management in the era of in vitro fertilization/intracytoplasmic sperm injection. Asian J Androl. 2016;18(3):343–8.CrossRefPubMedPubMedCentral
Metadata
Title
An association between sperm PLCζ levels and varicocele?
Authors
Elham Janghorban-Laricheh
Nasim Ghazavi-Khorasgani
Marziyeh Tavalaee
Dina Zohrabi
Homayon Abbasi
Mohammad H. Nasr- Esfahani
Publication date
01-12-2016
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 12/2016
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-016-0802-5

Other articles of this Issue 12/2016

Journal of Assisted Reproduction and Genetics 12/2016 Go to the issue

Review

The state of “freeze-for-all” in human ARTs

Editor’s Commentary

On measuring advances in human ARTs, one step at a time

Meeting Abstracts

Abstracts from the Translational Reproductive Biology and Clinical Reproductive Endocrinology Conference held Novembrer 17–20, 2016

Review

Improvement of gamete quality by stimulating and feeding the endogenous antioxidant system: mechanisms, clinical results, insights on gene-environment interactions and the role of diet

Fertility Preservation

Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in SCID mice: dynamics and molecular aspects

Fertility Preservation

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model