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Incidence of Y chromosome microdeletions in patients with Klinefelter syndrome

  • F. Sciarra
  • M. Pelloni
  • F. Faja
  • F. Pallotti
  • G. Martino
  • A. F. Radicioni
  • A. Lenzi
  • F. Lombardo
  • D. PaoliEmail author
Original Article

Abstract

Purpose

The aim of this study was to study the incidence of Y chromosome microdeletions in a Caucasian population of Klinefelter syndrome (KS) patients and to investigate the possible association between Y chromosome microdeletions and KS.

Materials and methods

We conducted a retrospective study on 118 KS patients, 429 patients with non-obstructive azoospermia (NOA), and 155 normozoospermic men. Eight of the 118 KS patients had undergone testicular sperm extraction (TESE). All patients underwent semen examination and Y chromosome microdeletions evaluated by PCR, using specific sequence tagged site (STS) primer sets, which spanned the azoospermia factor AZFa, AZFb, and AZFc regions of the Y chromosome.

Results

Semen analysis of the KS group revealed: 1 patient with oligozoospermia, 1 with severe oligoasthenoteratozoospermia, 2 with cryptozoospermia, and 114 with azoospermia. Eight of the 114 azoospermic KS patients underwent TESE, and spermatozoa were recovered from three of these, all of whom had non-mosaic karyotype 47, XXY. 10.7% of the NOA patients presented AZF microdeletions. In 429 cases with NOA, 8 cases had AZFa + b + c deletion, 6 cases had AZF b + c deletion, 4 cases had AZFa microdeletion, 8 cases had AZFb microdeletion, and 20 cases had AZFc microdeletion. Just one KS patient (0.8%) presented microdeletion in the AZFc region.

Conclusion

The percentage of microdeletions in KS patients was lower than in NOA patients, suggesting that AZF microdeletions and KS do not have a causal relationship and that Y chromosome microdeletions are not a genetic factor linked to KS.

Keywords

Klinefelter syndrome Non-obstructive azoospermia Y chromosome microdeletions 

Notes

Acknowledgements

The authors wish to thank Marie-Hélène Hayles for her assistance in the English translation of the manuscript.

Author contributions

DP, AFR, and FL: conception and design of the study; MP, FS, FF, and GM: acquisition of data; FP, DP: analysis and interpretation of data; FS and MP: drafting the article; AL, FL, and DP: revising it critically for important intellectual content and final approval of the version to be submitted.

Funding

This work was supported by a Grant from the Italian Ministry of Education and Research (MIUR-PRIN 2015- 2015XCR88M-006) and “Sapienza” University of Rome, Faculty of Medicine.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Sapienza University of Rome—Policlinico Umberto I Ethics Committee.

Informed consent

All participants signed informed consent.

References

  1. 1.
    Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E (2004) Klinefelter’s syndrome. Lancet 364:273–283CrossRefGoogle Scholar
  2. 2.
    Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A, Klinefelter ItaliaN Group (KING) (2017) Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Invest 40:123–134CrossRefGoogle Scholar
  3. 3.
    Bojesen A, Juul S, Gravholt CH (2003) Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 88:622–626CrossRefGoogle Scholar
  4. 4.
    Aksglaede L, Wikström AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A (2006) Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update 12:39–48CrossRefGoogle Scholar
  5. 5.
    Krausz C, Forti G (2006) Sperm cryopreservation in male infertility due to genetic disorders. Cell Tissue Bank. 7:105–112CrossRefGoogle Scholar
  6. 6.
    Thomas NS, Hassold TJ (2003) Aberrant recombination and the origin of Klinefelter syndrome. Hum Reprod Update 9:309–317CrossRefGoogle Scholar
  7. 7.
    Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E (2004) Klinefelter’s syndrome. Lancet 364:273–283CrossRefGoogle Scholar
  8. 8.
    Tüttelmann F, Gromoll J (2010) Novel genetic aspects of Klinefelter’s syndrome. Mol Hum Reprod 16:386–395CrossRefGoogle Scholar
  9. 9.
    Rajpert-De Meyts E, Ottesen AM, Garn ID, Aksglaede L, Juul A (2011) Deletions of the Y chromosome are associated with sex chromosome aneuploidy but not with Klinefelter syndrome. Acta Paediatr 100:900–902CrossRefGoogle Scholar
  10. 10.
    Ferlin A, Arredi B, Speltra E, Cazzadore C, Selice R, Garolla A, Lenzi A, Foresta C (2007) Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab 92:762–770CrossRefGoogle Scholar
  11. 11.
    Foresta C, Ferlin A, Moro E, Marin P, Rossi A, Scandellari C (2001) Microdeletion of chromosome Y in male infertility: role of the DAZ gene. Ann Ital Med Int 16:82–92PubMedGoogle Scholar
  12. 12.
    Mitra A, Dada R, Kumar R, Gupta NP, Kucheria K, Gupta SK (2006) Y chromosome microdeletions in azoospermic patients with Klinefelter’s syndrome. Asian J Androl 8:81–88CrossRefGoogle Scholar
  13. 13.
    Hadjkacem-Loukil L, Ghorbel M, Bahloul A, Ayadi H, Ammar-Keskes L (2009) Genetic association between AZF region polymorphism and Klinefelter syndrome. Reprod Biomed Online 19:547–551CrossRefGoogle Scholar
  14. 14.
    Ceylan C, Ceylan GG, Serel TA (2010) The azoospermia factor locus-c region was found to be related to Klinefelter syndrome in Turkish patients. Genet Mol Res 9:1229–1233CrossRefGoogle Scholar
  15. 15.
    Li LX, Dai HY, Ding XP, Zhang YP, Zhang XH, Ren HY, Chen ZY (2015) Investigation of AZF microdeletions in patients with Klinefelter syndrome. Genet Mol Res 14:15140–15147CrossRefGoogle Scholar
  16. 16.
    Tateno T, Sasagawa I, Ichiyanagi O, Ashida J, Nakada T, Saito H, Hiroi M (1999) Microdeletion of the DAZ (deleted in azoospermia) gene or the YRRM (Y chromosome ribonucleic acid recognition motif) gene does not occur in patients with Klinefelter’s syndrome with and without spermatogenesis. Fertil Steril 71:746–749CrossRefGoogle Scholar
  17. 17.
    Lee YH, Kim T, Kim MH, Kim YT, Kim SHY (2000) Chromosome microdeletions in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome. Exp Mol Med 32:231–234CrossRefGoogle Scholar
  18. 18.
    Ambasudhan R, Singh K, Agarwal JK, Singh SK, Khanna A, Sah RK, Singh I, Raman R (2003) Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion. J Biosci 28:605–612CrossRefGoogle Scholar
  19. 19.
    Choe JH, Kim JW, Lee JS, Seo JT (2007) Routine screening for classical azoospermia factor deletions of the Y chromosome in azoospermic patients with Klinefelter syndrome. Asian J Androl 9:815–820CrossRefGoogle Scholar
  20. 20.
    Balkan M, Tekes S, Gedik A (2008) Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey. J Assist Reprod Genet 25:559–565CrossRefGoogle Scholar
  21. 21.
    Behulova R, Varga I, Strhakova L, Bozikova A, Gabrikova D, Boronova I, Repiska V (2011) Incidence of microdeletions in the AZF region of the Y chromosome in Slovak patients with azoospermia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 155:33–38CrossRefGoogle Scholar
  22. 22.
    Simoni M, Tüttelmann F, Gromoll J, Nieschlag E (2008) Clinical consequences of microdeletions of the Y chromosome: the extended Münster experience. Reprod Biomed Online 16:289–303CrossRefGoogle Scholar
  23. 23.
    Zhang HG, Zhang ZB, Wang RX, Yu Y, Yu XW, Fadlalla E, Liu RZ (2013) Male infertility in Northeast China: molecular detection of Y chromosome microdeletions in azoospermic patients with Klinefelter’s syndrome. Genet Mol Res 12:4972–4980CrossRefGoogle Scholar
  24. 24.
    World Health Organization (1992) WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 3rd edn. Cambridge University Press, CambridgeGoogle Scholar
  25. 25.
    World Health Organization (1999) WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 4th edn. Cambridge University Press, CambridgeGoogle Scholar
  26. 26.
    World Health Organisation (2010) WHO laboratory manual for the examination and processing of human semen, 5th edn. Geneve, SwitzerlandGoogle Scholar
  27. 27.
    Van Assche E, Bonduelle M, Tournaye H, Joris H, Verheyen G, Devroey P, Van Steirteghem A, Liebaers I (1996) Cytogenetics of infertile men. Hum Reprod 4:1–24CrossRefGoogle Scholar
  28. 28.
    Vincent MC, Daudin M, De MP, Massat G, Mieusset R, Pontonnier F, Calvas P, Bujan L, Bourrouillout G (2002) Cytogenetic investigations of infertile men with low sperm counts: a 25-year experience. J Androl 23:18–22CrossRefGoogle Scholar
  29. 29.
    Aksglaede L, Juul A (2013) Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol 168:R67–R76CrossRefGoogle Scholar
  30. 30.
    Lin YM, Huang WJ, Lin JS, Kuo PL (2004) Progressive depletion of germ cells in a man with nonmosaic Klinefelter’s syndrome: optimal time for sperm recovery. Urol 63:380–381CrossRefGoogle Scholar
  31. 31.
    Aksglaede L, Jørgensen N, Skakkebaek NE, Juul A (2009) Low semen volume in 47 adolescents and adults with 47, XXY Klinefelter or 46, XX male syndrome). Int J Androl 32:376–384CrossRefGoogle Scholar
  32. 32.
    Emre Bakircioglu M, Erden HF, Kaplancan T, Ciray N, Bener F, Bahceci M (2006) Aging may adversely affect testicular sperm recovery in patients with Klinefelter syndrome. Urol 68:1082–1086CrossRefGoogle Scholar
  33. 33.
    Ichioka K, Utsunomiya N, Kohei N, Ueda N, Inoue K, Terai A (2006) Adult onset of declining spermatogenesis in a man with nonmosaic Klinefelter’s syndrome. Fertil Steril 85:1511CrossRefGoogle Scholar
  34. 34.
    Maiburg M, Repping S, Giltay J (2012) The genetic origin of Klinefelter syndrome and its effect on spermatogenesis. Fertil Steril 98:253–260CrossRefGoogle Scholar
  35. 35.
    Helena Mangs A, Morris BJ (2007) The human Pseudoautosomal region (PAR): origin, function and future. Curr Genom 8:129–136CrossRefGoogle Scholar
  36. 36.
    Freije D, Helms C, Watson MS, Donis-Keller H (1992) Identification of a second pseudoautosomal region near the Xq and Yq telomeres. Science 258:1784–1787CrossRefGoogle Scholar
  37. 37.
    Rappold GA (1993) The pseudoautosomal regions of the human sex chromosomes. Hum Genet 92:315–324CrossRefGoogle Scholar
  38. 38.
    Thomas NS, Collins AR, Hassold TJ, Jacobs PA (2000) A reinvestigation of non-disjunction resulting in 47, XXY males of paternal origin. Eur J Hum Genet 8:805–808CrossRefGoogle Scholar
  39. 39.
    van der Ven K, Montag M, Peschka B, Leygraaf J, Schwanitz G, Haidl G, Krebs D, van der Ven H (1997) Combined cytogenetic and Y chromosome microdeletion screening in males undergoing intracytoplasmic sperm injection. Mol Hum Reprod 3:699–704CrossRefGoogle Scholar
  40. 40.
    Foresta C, Ferlin A, Garolla A, Moro E, Pistorello M, Barbaux S, Rossato M (1998) High frequency of well-defined Y-chromosome deletions in idiopathic Sertoli cell-only syndrome. Hum Reprod 13:302–307CrossRefGoogle Scholar
  41. 41.
    Dada R, Gupta NP, Kucheria K (2002) AZF microdeletions associated with idiopathic and non-idiopathic cases with cryptorchidism and varicocele. Asian J Androl 4:259–263PubMedGoogle Scholar
  42. 42.
    Thangaraj K, Gupta NJ, Pavani K, Reddy AG, Subramainan S, Rani DS et al (2003) Y chromosome deletions in azoospermic men in India. J Androl 24:588–597CrossRefGoogle Scholar
  43. 43.
    Chiang HS, Yeh SD, Wu CC, Huang BC, Tsai HJ, Fang CL (2004) Clinical and pathological correlation of the microdeletion of Y chromosome for the 30 patients with azoospermia and severe oligoasthenospermia. Asian J Androl 6:369–375PubMedGoogle Scholar
  44. 44.
    Li Z, Haines CJ, Han Y (2008) “Micro-deletions” of the human Y chromosome and their relationship with male infertility. J Genet Genomics 35:193–199CrossRefGoogle Scholar
  45. 45.
    Wang Rui-Xue, Chao Fu, Yang Ya-Ping, Han Rong-Rong, Dong Yuan, Dai Ru-Lin, Liu Rui-Zhi (2010) Male infertility in China: laboratory finding for AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China. J Assist Reprod Genet 27:391–396CrossRefGoogle Scholar
  46. 46.
    Ferrás C, Fernandes S, Marques CJ, Carvalho F, Alves C, Silva J, Sousa M, Barros A (2004) AZF and DAZ gene copy-specific deletion analysis in maturation arrest and Sertoli cell-only syndrome. Mol Hum Reprod 10:755–761CrossRefGoogle Scholar
  47. 47.
    Ferlin A, Tessari A, Ganz F, Marchina E, Barlati S, Garolla A (2005) Association of partial AZFc region deletions with spermatogenic impairment and male infertility. J Med Genet 42:209–213CrossRefGoogle Scholar
  48. 48.
    Zhang F, Lu C, Li Z, Xie P, Xia Y, Zhu X, Wu B, Cai X, Wang X, Qian J, Wang X, Jin L (2007) Partial deletions are associated with an increased risk of complete deletion in AZFc: a new insight into the role of partial AZFc deletions in male infertility. J Med Genet 44:437–444CrossRefGoogle Scholar
  49. 49.
    Arruda JT, Bordin BM, Santos PR, Mesquita WE, Silva RC, Maia MC, Approbato MS, Florêncio RS, Amaral WN, Rocha Filho MA, Moura KK (2007) Y chromosome microdeletions in Brazilian fertility clinic patients. Genet Mol Res 6:461–469PubMedGoogle Scholar
  50. 50.
    Krausz C, Rajpert-De Meyts E, Frydelund-Larsen L, Quintana-Murci L, McElreavey K, Skakkebaek NE (2001) Double-blind Y chromosome microdeletion analysis in men with known sperm parameters and reproductive hormone profiles: microdeletions are specific for spermatogenic failure. J Clin Endocrinol Metab 86:2638–2642PubMedGoogle Scholar
  51. 51.
    Colaco S, Modi D (2018) Genetics of the human Y chromosome and its association with male infertility. Reprod Biol Endocrinol. 16:14CrossRefGoogle Scholar
  52. 52.
    Stouffs K, Lissens W, Tournaye H, Haentjens P (2011) What about gr/gr deletions and male infertility? Systematic review and meta-analysis. Hum Reprod Update 17:197–209CrossRefGoogle Scholar
  53. 53.
    Hucklenbroich K, Gromoll J, Heinrich M, Hohoff C, Nieschlag E, Simoni M (2005) Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis. Hum Reprod 20:191–197CrossRefGoogle Scholar
  54. 54.
    Krausz C, Casamonti E (2017) Spermatogenic failure and the Y chromosome. Hum Genet 136:637–655CrossRefGoogle Scholar
  55. 55.
    Bansal SK, Gupta G, Rajender S (2016) Y chromosome b2/b3 deletions and male infertility: a comprehensive meta-analysis, trial sequential analysis and systematic review. Mutat Res Rev Mutat 768:78–90CrossRefGoogle Scholar
  56. 56.
    Radicioni AF, Ferlin A, Balercia G, Pasquali D, Vignozzi L, Maggi M, Foresta C, Lenzi A (2010) Consensus statement on diagnosis and clinical management of Klinefelter syndrome. J Endocrinol Invest 33:839–850CrossRefGoogle Scholar
  57. 57.
    Ciocca G, Limoncin E, Mollaioli D, Gravina GL, Carosa E, Di Sante S, Gianfrilli D, Lombardo F, Lenzi A, Jannini EA (2015) SIAMS survey on sexological screening during the assisted reproductive technologies in Italy. J Endocrinol Invest 38:999–1005CrossRefGoogle Scholar
  58. 58.
    Roli L, Santi D, Belli S, Tagliavini S, Cavalieri S, De Santis MC, Baraldi E, Fanelli F, Mezzullo M, Granata AR, Pagotto U, Pasquali R, Rochira V, Carani C, Simoni M, Trenti T (2017) The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry. J Endocrinol Invest 40:841–850CrossRefGoogle Scholar
  59. 59.
    Peterlin B, Kunej T, Sinkovec J, Gligorievska N, Zorn B (2002) Screening for Y chromosome microdeletions in 226 Slovenian subfertile men. Hum Reprod 17:17–24CrossRefGoogle Scholar
  60. 60.
    Oates RD, Silber S, Brown LG, Page DC (2002) Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome, and of 18 children conceived via ICSI. Hum Reprod 17:2813–2824CrossRefGoogle Scholar
  61. 61.
    Mitra A, Dada R, Kumar R, Gupta NP, Kucheria K, Gupta SK (2008) Screening for Y-chromosome microdeletions in infertile Indian males: utility of simplified multiplex PCR. Indian J Med Res 127:124–132PubMedGoogle Scholar
  62. 62.
    Zaimy MA, Kalantar SM, Sheikhha MH, Jahaninejad T, Pashaiefar H, Ghasemzadeh J, Zahraei M (2013) The frequency of Yq microdeletion in azoospermic and oligospermic Iranian infertile men. Iran J Reprod Med 11:453–458PubMedPubMedCentralGoogle Scholar
  63. 63.
    Bahmanimehr A, Zeighami S, Namavar Jahromi B, Anvar Z, Parsanezhad ME, Davari M, Montazeri S (2018) Detection of Y chromosome microdeletions and hormonal profile analysis of infertile men undergoing assisted reproductive technologies. Int J Fertil Steril 12:173–177PubMedPubMedCentralGoogle Scholar
  64. 64.
    Denschlag D, Tempfer C, Kunze M, Wolff G, Keck C (2004) Assisted reproductive techniques in patients with Klinefelter syndrome: a critical review. Fertil Steril 82:775–779CrossRefGoogle Scholar
  65. 65.
    Okada H, Goda K, Yamamoto Y, Sofikitis N, Miyagawa I, Mio Y, Koshida M, Horie S (2005) Age as a limiting factor for successful sperm retrieval in patients with nonmosaic Klinefelter’s syndrome. Fertil Steril 84:1662–1664CrossRefGoogle Scholar
  66. 66.
    Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, Ferlin A, Foresta C, Jannini EA, Maggi M, Lenzi A, Pasquali D, Francavilla S, Klinefelte ItaliaN Group (KING) (2017) Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis. Hum Reprod Update 23:265–275CrossRefGoogle Scholar
  67. 67.
    Bakircioglu ME, Ulug Ulun, Erden Halit Firat, Tosun Suleyman, Asina Bayram BS, Ciray Nadir, Bahceci Mustafa (2011) Klinefelter syndrome: does it confer a bad prognosis in treatment of nonobstructive azoospermia? Fertil Steril 95:1696–1699CrossRefGoogle Scholar
  68. 68.
    Madureira C, Cunha M, Sousa M, Neto AP, Pinho MJ, Viana P, Gonçalves A, Silva J, Teixeira da Silva J, Oliveira C, Ferraz L, Dória S, Carvalho F, Barros A (2014) Treatment by testicular sperm extraction and intracytoplasmic sperm injection of 65 azoospermic patients with non-mosaic Klinefelter syndrome with birth of 17 healthy children. Andrology 2:623–631CrossRefGoogle Scholar
  69. 69.
    Staessen C, Tournaye H, Van Assche E, Michiels A, Van Landuyt L, Devroey P, Liebaers I, Van Steirteghem A (2003) PGD in 47, XXY Klinefelter’s syndrome patients. Hum Reprod Update 9:319–330CrossRefGoogle Scholar
  70. 70.
    Komori S, Kato H, Kobayashi S, Koyama K, Isojima S (2002) Transmission of Y chromosomal microdeletions from father to son through intracytoplasmic sperm injection. J Hum Genet 47:465–468CrossRefGoogle Scholar
  71. 71.
    Zhang F, Lu C, Li Z, Xie P, Xia Y, Zhu X, Wu B, Cai X, Wang X, Qian J, Wang X, Jin L (2007) Partial deletions are associated with an increased risk of complete deletion in AZFc: a new insight into the role of partial AZFc deletions in male infertility. J Med Genet 44:437–444CrossRefGoogle Scholar
  72. 72.
    Plaseski T, Noveski P, Trivodalieva S, Efremov GD, Plaseska-Karanfilska D (2008) Quantitative fluorescent-PCR detection of sex chromosome aneuploidies and AZF deletions/duplications. Genet Test 12:595–605CrossRefGoogle Scholar
  73. 73.
    Oliva R, Margarit E, Ballescá JL, Carrió A, Sánchez A, Milà M, Jiménez L, Alvarez-Vijande JR, Ballesta F (1998) Prevalence of Y chromosome microdeletions in oligospermic and azoospermic candidates for intracytoplasmic sperm injection. Fertil Steril 70:506–510CrossRefGoogle Scholar
  74. 74.
    Pina-Neto JM, Carrara RC, Bisinella R, Mazzucatto LF, Martins MD, Sartoratto E et al (2006) Somatic cytogenetic and azoospermia factor gene microdeletion studies in infertile men. Braz J Med Biol Res 39:555–561CrossRefGoogle Scholar
  75. 75.
    Mohammed F, Al-Yatama F, Al-Bader M, Tayel SM, Gouda S, Naguib KK (2007) Primary male infertility in Kuwait: a cytogenetic and molecular study of 289 infertile Kuwaiti patients. Andrologia 39:87–92CrossRefGoogle Scholar
  76. 76.
    Dos Santos Godoy GC, Galera BB, Araujo C, Barbosa JS, de Pinho MF, Galera MF, de Medeiros SF (2014) The Low prevalence of Y chromosomal microdeletions is observed in the oligozoospermic men in the area of Mato Grosso State and Amazonian Region of Brazilian patients. Clin Med Insights Reprod Health 8:51–57PubMedPubMedCentralGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2018

Authors and Affiliations

  • F. Sciarra
    • 1
  • M. Pelloni
    • 1
  • F. Faja
    • 1
  • F. Pallotti
    • 1
  • G. Martino
    • 2
  • A. F. Radicioni
    • 3
  • A. Lenzi
    • 1
  • F. Lombardo
    • 1
  • D. Paoli
    • 1
    Email author
  1. 1.Laboratory of Seminology-Sperm Bank “Loredana Gandini”, Department of Experimental Medicine“Sapienza” University of RomeRomeItaly
  2. 2.Department of Surgical Sciences “R. Paolucci”“Sapienza” University of RomeRomeItaly
  3. 3.Hormone Laboratory, Department of Experimental Medicine, Medical Pathophysiology Section“Sapienza” University of RomeRomeItaly

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