Semen Biochemical Components in Varicocele, Leukocytospermia, and Idiopathic Infertility

Giulia Collodel, Cinzia Signorini, Fabiola Nerucci, Laura Gambera, Francesca Iacoponi, Elena Moretti, Giulia Collodel, Cinzia Signorini, Fabiola Nerucci, Laura Gambera, Francesca Iacoponi, Elena Moretti

Abstract

The evaluation of the seminal plasma plays a relevant role in the definition of male infertility and in assisted reproduction outcomes; for this reason, it would be recommended to find biochemical markers able to characterize sperm pathology. In this study, 53 infertile patients (grouped by the presence leukocytospermia, idiopathic infertility, or varicocele) and 10 fertile men were selected. Spermiogram was performed by light microscopy, and sperm ultrastructure was evaluated by transmission electron microscopy (TEM) mathematically elaborated. Testosterone (TESTO), estradiol (E2), ferritin (FERR), iron (Fe), transferrin (TRSF), triglycerides (TRG), cholesterol (CHOL), and isoprostanes (F2-IsoPs) were detected in seminal plasma. Sperm characteristics and biochemical components were correlated by Spearman's rank correlation coefficient in the whole population and in each group. The levels of TESTO and E2 were positively correlated with sperm quality in particular, and E2 was correlated with fertility index expressing the number of sperm free of ultrastructural defects evaluated by TEM. On the contrary, the indices of iron metabolism (FERR, Fe, and TRSF) were positively associated with low sperm quality and sperm necrosis, particularly in leukocytospermia and varicocele groups, pathologies in which an inflammatory status and oxidative stress condition are present. The study of the seminal plasma composition deserves attention because the levels of the various components seem to be associated with specific reproductive pathologies.

Keywords: Iron metabolism; Isoprostanes; Leukocytospermia; TEM; Testosterone; Varicocele.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
TEM micrographs of longitudinal sections of spermatozoa. In a, two necrotic spermatozoa are shown, the chromatin (dCh) appears disrupted, the plasma membranes are broken (arrow), and the axonemal components are absent (aAx). An immature sperm is represented in b, the chromatin is uncondensed (uCh), the acrosome (A) reduced and far from the nucleus, the tail is coiled into a cytoplasmic residue (CR), and mitochondria (M) are disassembled. An apoptotic sperm is shown in c, the chromatin is marginated (mCh), the tail is coiled but the axonemal components are well assembled (Ax); acrosome (A); and cytoplasmic residue (CR). ac Bar, 1 μm

References

    1. Feng RX, Lu JC, Zhang HY, Lü NQ. A pilot comparative study of 26 biochemical markers in seminal plasma and serum in infertile men. Biomed Res Int. 2015;2015:805328.
    1. Zhang HY, Lu JC, Feng RX. Correlations of 24 biochemical markers in seminal plasma with routine semen parameters. Zhonghua Nan Ke Xue. 2015;21(12):1087–1092.
    1. Camargo M, Intasqui P, Bertolla RP. Understanding the seminal plasma proteome and its role in male fertility. Basic Clin Androl. 2018;28:6.
    1. Recuero S, Fernandez-Fuertes B, Bonet S, Barranco I, Yeste M. Potential of seminal plasma to improve the fertility of frozen-thawed boar spermatozoa. Theriogenology. 2019;137:36–42.
    1. Vickram AS, Kamini AR, Das R, Pathy MR, Parameswari R, Sridharan TB. Validation of artificial neural network models for predicting biochemical markers associated with male infertility. Syst Biol Reprod Med. 2016;62(4):258–265.
    1. Tvrda E, Peer R, Sikka SC, Agarwal A. Iron and copper in male reproduction: a double-edged sword. J Assist Reprod Genet. 2015;32(1):3–16.
    1. Hashemi MM, Behnampour N, Nejabat M, Tabandeh A, Ghazi-Moghaddam B, Joshaghani HR. Impact of seminal plasma trace elements on human sperm motility parameters. Rom J Intern Med. 2018;56(1):15–20.
    1. Kleven MD, Jue S, Enns CA. The transferrin receptors, TfR1 and TfR2 bind transferrin through differing mechanisms. Biochemistry. 2018;57(9):1552–1559.
    1. Barthelemy C, Khalfoun B, Guillaumin JM, Lecomte P, Bardos P. Seminal fluid transferrin as an index of gonadal function in men. J Reprod Fertil. 1998;82(1):113–118.
    1. Matsuzaki M, Mizushima S, Dohra H, Sasanami T. Expression of transferrin and albumin in the sperm-storage tubules of Japanese quail and their possible involvement in long-term sperm storage. J Poult Sci. 2020;57(1):88–96.
    1. Silva GP, De La Vega Elena CD, Pirani Carneiro F, Russomano Veiga JP. Effect of systemic inflammation on level of ferritin seminal in chronic renal male patient undergoing hemodialysis. Int Arch Med. 2014;7:23.
    1. Murgia F, Corda V, Serrenti M, et al. Seminal fluid metabolomic markers of oligozoospermic infertility in humans. Metabolites. 2020;10(2):E64.
    1. Leahy T, Gadella BM. New insights into the regulation of cholesterol efflux from the sperm membrane. Asian J Androl. 2015;17(4):561–567.
    1. Vitku J, Kolatorova L, Hampl R. Occurrence and reproductive roles of hormones in seminal plasma. Basic Clin Androl. 2017;27:19.
    1. O'Donnell L, Robertson KM, Jones ME, Simpson ER. Estrogen and spermatogenesis. Endocr Rev. 2001;22(3):289–318.
    1. Zhang Q, Bai Q, Yuan Y, Liu P, Qiao J. Assessment of seminal estradiol and testosterone levels as predictors of human spermatogenesis. J Androl. 2010;31(2):215–20.
    1. Collodel G, Nerucci F, Signorini C, Iacoponi F, Moretti E. Associations between biochemical components of human semen with seminal conditions. Syst Biol Reprod Med. 2019;65(2):155–163.
    1. Benedetti S, Tagliamonte MC, Catalani S, Primiterra M, Canestrari F, De Stefani S, et al. Differences in blood and semen oxidative status in fertile and infertile men, and their relationship with sperm quality. Reprod BioMed Online. 2012;25(3):300–306.
    1. Nenkova G, Petrov L, Alexandrova A. Role of trace elements for oxidative status and quality of human sperm. Balkan Med J. 2017;34(4):343–348.
    1. Collodel G, Moretti E, Longini M, Pascarelli NA, Signorini C. Increased F2-isoprostane levels in semen and immunolocalization of the 8-Iso prostaglandin F2α in spermatozoa from infertile patients with varicocele. Oxidative Med Cell Longev. 2018;2018:7508014.
    1. World Health Organization . WHO laboratory manual for the examination and processing of human semen. 5. Geneva: WHO Press; 2010.
    1. Collodel G, Capitani S, Iacoponi F, Federico MG, Pascarelli NA, Moretti E. Retrospective assessment of potential negative synergistic effects of varicocele and tobacco use on ultrastructural sperm morphology. Urology. 2009;74(4):794–799.
    1. Baccetti B, Bernieri G, Burrini AG, Collodel G, Crisà N, Mirolli M, Moretti E, Piomboni P. Notulae Seminologicae. 5. Mathematical evaluation of interdependent submicroscopic sperm alterations. J Androl. 1995;16(4):356–371.
    1. Collodel G, Moretti E. Morphology and meiotic segregation in spermatozoa from men of proven fertility. J Androl. 2008;29(1):106–114.
    1. Stafforini DM, Sheller JR, Blackwell TS, Sapirstein A, Yull FE, McIntyre TM, et al. Release of free F2-iso-prostanes from esterified phospholipids is catalyzed by intracellular and plasma platelet-activating factor acetylhydrolases. J Biol Chem. 2006;281(8):4616–4623.
    1. Signorini C, De Felice C, Durand T, et al. Relevance of 4-F(4t)-neuroprostane and 10-F(4t)-neuroprostane to neurological diseases. Free Radic Biol Med. 2018;115:278–287.
    1. Signorini C, Cardile V, Pannuzzo G, Graziano ACE, Durand T, Galano JM, Oger C, Leoncini S, Cortelazzo A, Lee JCY, Hayek J, de Felice C. Increased isoprostanoid levels in brain from murine model of Krabbe disease—relevance of isoprostanes, dihomo-isoprostanes and neuroprostanes to disease severity. Free Radic Biol Med. 2019;139:46–54.
    1. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–245.
    1. Lazzarino G, Listorti I, Muzii L, Amorini AM, Longo S, di Stasio E, Caruso G, D’Urso S, Puglia I, Pisani G, Lazzarino G, Tavazzi B, Bilotta P. Low-molecular weight compounds in human seminal plasma as potential biomarkers of male infertility. Hum Reprod. 2018;33(10):1817–1828.
    1. Collodel G, Moretti E, Micheli L, Menchiari A, Moltoni L, Cerretani D. Semen characteristics and malondialdehyde levels in men with different reproductive problems. Andrology. 2015;3:280–286.
    1. Micheli L, Cerretani D, Collodel G, Menchiari A, Moltoni L, Fiaschi AI, Moretti E. Evaluation of enzymatic and non-enzymatic antioxidants in seminal plasma of men with genitourinary infections, Varicocele and Idiopathic Infertility. Andrology. 2016;4(3):456–464.
    1. Moretti E, Sutera G, Collodel G. The importance of transmission electron microscopy analysis of spermatozoa: diagnostic applications and basic research. Syst Biol Reprod Med. 2016;62(3):171–183.
    1. Gatimel N, Moreau, Parinaud J, Léandri RD. Sperm morphology: assessment, pathophysiology, clinical relevance, and state of the art in 2017. Andrology. 2017;5(5):845–886.
    1. Behrouzi B, Kenigsberg S, Alladin N, Swanson S, Zicherman J, Hong SH, Moskovtsev SI, Librach CL. Evaluation of potential protein biomarkers in patients with high sperm DNA damage. Syst Biol Reprod Med. 2013;59(3):153–163.
    1. Mirnamniha M, Faroughi F, Tahmasbpour E, Ebrahimi P, Harchegani AB. An overview on role of some trace elements in human reproductive health, sperm function and fertilization process. Rev Environ Health. 2019;34(4):339–348.
    1. Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Semin Cell Dev Biol. 2014;30:2–13.
    1. Thanaboonyawat I, Chantrapanichkul P, Petyim S, Kaewjunun C, Laokirkkiat P, Choavaratana R. Application of testosterone supplementation in semen to improve sperm motility in asthenozoospermic males. Arch Gynecol Obstet. 2017;296(3):589–596.
    1. Idaomar M, Guerin JF, Lorange J, Cziba JC. Stimulation of motility and energy metabolism of spermatozoa from astenozoospermic patients by 17β-estradiol. Arch Androl. 1989;22:197–202.
    1. Baldi E, Luconi M, Bonaccorsi L, Muratori M, Forti G. Intracellular events and signaling pathways involved in sperm acquisition of fertilizing capacity and acrosome reaction. Front Biosci. 2000;5:110–123.
    1. Aquila S, Sisci D, Gentile M, Carpino A, Middea E, Catalano S, et al. Towards a physiological role for cytochrome P450 aromatase in ejaculated human sperm. Hum Reprod. 2003;18(8):1650–1659.
    1. Cooke PS, Nanjappa MK, Ko CM, Gail S, Prins GS, Hess RA. Estrogens in male physiology. Physiol Rev. 2017;97(3):995–1043.
    1. Agarwal A, Rana M, Qiu E, AlBunni H, Bui AD, Henkel R. Role of oxidative stress, infection and inflammation in male infertility. Andrologia. 2018;50(11):e13126.
    1. Chao KC, Chang CC, Chiou HY, Chang JS. Serum ferritin is inversely correlated with testosterone in boys and young male adolescents: a cross-sectional study in Taiwan. PLoS One. 2015;10(12):e0144238.
    1. Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017;29(9):401–409.
    1. Tremellen K, McPhee N, Pearce K, Benson S, Schedlowski M, Engler H. Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age. Am J Physiol Endocrinol Metab. 2018;314(3):E206–E213.
    1. Ueda N, Takasawa K. Impact of inflammation on ferritin, hepcidin and the management of iron deficiency anemia in chronic kidney disease. Nutrients. 2018;10(9):1173.
    1. Darbandi M, Darbandi S, Agarwal A, Sengupta P, Durairajanayagam D, Henkel R, Sadeghi MR. Reactive oxygen species and male reproductive hormones. Reprod Biol Endocrinol. 2018;16:87.
    1. Zorn B, Ihan A, Kopitar AN, Kolbezen M, Sesek-Briski A, Meden-Vrtovec H. Changes in sperm apoptotic markers as related to seminal leukocytes and elastase. Reprod Biomed Online. 2010;21(1):84–92.
    1. Moretti E, Collodel G, Mazzi L, Campagna MS, Iacoponi F, Mazzi L, et al. Resistin, interleukin-6, tumor necrosis factor-alpha, and human semen parameters in the presence of leukocytospermia, smoking habit, and varicocele. Fertil Steril. 2014;102(2):354–360.
    1. Ammar O, Houas Z, Mehdi M. The association between iron, calcium, and oxidative stress in seminal plasma and sperm quality. Environ Sci Pollut Res Int. 2019;26(14):14097–14105.
    1. Koeva YA. Immunoreactivity for ferritin in Leydig cells of human testis. Folia Med (Plovdiv) 2002;44(3):24–26.
    1. Mikuz G. The multitasking Sertoli cell. Pathologe. 2019;40(Suppl):318–324.
    1. Lécureuil C, Staub C, Fouchécourt S, Maurel MC, Fontaine I, Martinat N, Gauthier C, Daudignon A, Delaleu B, Sow A, Jégou B, Guillou F. Transferrin overexpression alters testicular function in aged mice. Mol Reprod Dev. 2007;74(2):197–206.
    1. Longini M, Moretti E, Signorini C, Noto D, Iacoponi F, Collodel G. Relevance of seminal F2-dihomo-IsoPs, F2-IsoPs and F4-NeuroPs in idiopathic infertility and varicocele. Prostaglandins Other Lipid Mediat. 2020;149:106448.
    1. Lu JC, Jing J, Yao Q, Fan K, Wang GH, Feng RX, Liang YJ, Chen L, Ge YF, Yao B. Relationship between lipids levels of serum and seminal plasma and semen parameters in 631 Chinese subfertile men. PLoS One. 2016;11(1):e0146304.
    1. Lu JC, Jing J, Chen L, Ge YF, Feng RX, Liang YJ, Yao B. Analysis of human sperm DNA fragmentation index (DFI) related factors: a report of 1010 subfertile men in China. Reprod Biol Endocrinol. 2018;16(1):23.
    1. Saez Lancellotti TE, Boarelli PV, Monclus MA, Cabrillana ME, Clementi MA, Espínola LS, Cid Barría JL, Vincenti AE, Santi AG, Fornés MW. Hypercholesterolemia impaired sperm functionality in rabbits. PLoS One. 2010;5(1):e13457.
    1. Tournaye H, Krausz C, Oates RD. Novel concepts in the aetiology of male reproductive impairment. Lancet Diabetes Endocrinol. 2016;8587:1–10.
    1. Bracke A, Peeters K, Punjabi U, Hoogewijs D, Dewilde S. A search for molecular mechanisms underlying male idiopathic infertility. Reprod Biomed Online. 2018;36(3):327–339.

Source: PubMed

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