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

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Urology Reports
Published in: Current Urology Reports 10/2016

01-10-2016 | Men’s Health (A Dabaja, Section Editor)

Genetics of Male Infertility

Authors: Filipe Tenorio Lira Neto, Phil Vu Bach, Bobby Baback Najari, Philip Shihua Li, Marc Goldstein

Published in: Current Urology Reports | Issue 10/2016

Login to get access

Abstract

While 7 % of the men are infertile, currently, a genetic etiology is identified in less than 25 % of those men, and 30 % of the infertile men lack a definitive diagnosis, falling in the “idiopathic infertility” category. Advances in genetics and epigenetics have led to several proposed mechanisms for male infertility. These advances may result in new diagnostic tools, treatment approaches, and better counseling with regard to treatment options and prognosis. In this review, we focus on clinical aspects of male infertility and the role of genetics in elucidating etiologies and the potential of treatments.
Literature
1.
Thoma ME, McLain AC, Louis JF, King RB, Trumble AC, Sundaram R, et al. Prevalence of infertility in the united states as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013;99:1324–31. e1321.PubMedPubMedCentralCrossRef
2.
Sabanegh Jr E, Agarwal A. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, editors. Campbell-walsh urology, vol. 1. Philadelphia: Elsevier Saunders; 2016.
3.
4.
Ferlin A, Raicu F, Gatta V, Zuccarello D, Palka G, Foresta C. Male infertility: role of genetic background. Reprod Biomed Online. 2007;14:734–45.PubMedCrossRef
5.
Gonsalves J, Sun F, Schlegel PN, Turek PJ, Hopps CV, Greene C, et al. Defective recombination in infertile men. Hum Mol Genet. 2004;13:2875–83.PubMedCrossRef
6.••
Ramasamy R, Scovell JM, Kovac JR, Cook PJ, Lamb DJ, Lipshultz LI. Fluorescence in situ hybridization detects increased sperm aneuploidy in men with recurrent pregnancy loss. Fertil Steril. 2015;103:906–9. e901. Original article demonstrating genetic sperm alteration in men with recurrent preganacy loss and normal semen analiysis paramenters.
7.
8.•
Groth KA, Skakkebaek A, Host C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome—a clinical update. J Clin Endocrinol Metab. 2013;98:20–30. Excelent review about other clinical aspects of Klinefelter syndrome that are usually overlooked.PubMedCrossRef
9.
Stahl PJ, Schlegel PN. Genetic evaluation of the azoospermic or severely oligozoospermic male. Curr Opin Obstet Gynecol. 2012;24:221–8.PubMedCrossRef
10.
Iitsuka Y, Bock A, Nguyen DD, Samango-Sprouse CA, Simpson JL, Bischoff FZ. Evidence of skewed x-chromosome inactivation in 47, XXY and 48, XXYY Klinefelter patients. Am J Med Genet. 2001;98:25–31.PubMedCrossRef
11.
Samplaski MK, Lo KC, Grober ED, Millar A, Dimitromanolakis A, Jarvi KA. Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients. Fertil Steril. 2014;101:950–5.PubMedCrossRef
12.
Wosnitzer MS, Paduch DA. Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome. Am J Med Genet C: Semin Med Genet. 2013;163C:16–26.CrossRef
13.
D’Aurora M, Ferlin A, Di Nicola M, Garolla A, De Toni L, Franchi S, et al. Deregulation of sertoli and leydig cells function in patients with Klinefelter syndrome as evidenced by testis transcriptome analysis. BMC Genomics. 2015;16:156.PubMedPubMedCentralCrossRef
14.
Aksglaede L, Wikstrom AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update. 2006;12:39–48.PubMedCrossRef
15.
Kotula-Balak M, Bablok L, Fracki S, Jankowska A, Bilinska B. Immunoexpression of androgen receptors and aromatase in testes of patient with Klinefelter’s syndrome. Folia Histochem Cytobiol. 2004;42:215–20.PubMed
16.
Yu YH, Siao FP, Hsu LC, Yen PH. Tex11 modulates germ cell proliferation by competing with estrogen receptor beta for the binding to HPIP. Mol Endocrinol (Baltimore, Md). 2012;26:630–42.CrossRef
17.
Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E. X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J Clin Endocrinol Metab. 2004;89:6208–17.PubMedCrossRef
18.
Tuttelmann F, Damm OS, Luetjens CM, Baldi M, Zitzmann M, Kliesch S, et al. Intratesticular testosterone is increased in men with Klinefelter syndrome and may not be released into the bloodstream owing to altered testicular vascularization—a preliminary report. Andrology. 2014;2:275–81.PubMedCrossRef
19.
Mehta A, Bolyakov A, Roosma J, Schlegel PN, Paduch DA. Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor. Fertil Steril. 2013;100:970–4.PubMedCrossRef
20.
Madureira C, Cunha M, Sousa M, Neto AP, Pinho MJ, Viana P, et al. 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. 2014;2:623–31.PubMedCrossRef
21.
Lenz P, Luetjens CM, Kamischke A, Kuhnert B, Kennerknecht I, Nieschlag E. Mosaic status in lymphocytes of infertile men with or without Klinefelter syndrome. Human Reprod (Oxford, England). 2005;20:1248–55.CrossRef
22.
Foresta C, Galeazzi C, Bettella A, Marin P, Rossato M, Garolla A, et al. Analysis of meiosis in intratesticular germ cells from subjects affected by classic Klinefelter’s syndrome. J Clin Endocrinol Metab. 1999;84:3807–10.PubMed
23.
Abramsky L, Chapple J. 47, xxy (klinefelter syndrome) and 47, xyy: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling. Prenat Diagn. 1997;17:363–8.PubMedCrossRef
24.
Bardsley MZ, Kowal K, Levy C, Gosek A, Ayari N, Tartaglia N, et al. 47, xyy syndrome: clinical phenotype and timing of ascertainment. J Pediatr. 2013;163:1085–94.PubMedPubMedCentralCrossRef
25.
Abdel-Razic MM, Abdel-Hamid IA, ElSobky ES. Nonmosaic 47, xyy syndrome presenting with male infertility: case series. Andrologia. 2012;44:200–4.PubMedCrossRef
26.
Skakkebaek NE, Hulten M, Jacobsen P, Mikkelsen M. Quantification of human seminiferous epithelium. Ii. Histological studies in eight 47, xyy men. J Reprod Fertil. 1973;32:391–401.PubMedCrossRef
27.
Gonzalez-Merino E, Hans C, Abramowicz M, Englert Y, Emiliani S. Aneuploidy study in sperm and preimplantation embryos from nonmosaic 47, xyy men. Fertil Steril. 2007;88:600–6.PubMedCrossRef
28.
Wu C, Wang L, Iqbal F, Jiang X, Bukhari I, Guo T, et al. Preferential y-y pairing and synapsis and abnormal meiotic recombination in a 47, xyy man with non obstructive azoospermia. Mol Cytogenet. 2016;9:9.PubMedPubMedCentralCrossRef
29.
Mau-Holzmann UA. Somatic chromosomal abnormalities in infertile men and women. Cytogenet Genome Res. 2005;111:317–36.PubMedCrossRef
30.
31.
Li TF, Wu QY, Zhang C, Li WW, Zhou Q, Jiang WJ, et al. 46, xx testicular disorder of sexual development with sry-negative caused by some unidentified mechanisms: a case report and review of the literature. BMC Urol. 2014;14:104.PubMedPubMedCentralCrossRef
32.
Hyon C, Chantot-Bastaraud S, Harbuz R, Bhouri R, Perrot N, Peycelon M, et al. Refining the regulatory region upstream of sox9 associated with 46, xx testicular disorders of sex development (dsd). Am J Med Genet A. 2015;167A:1851–8.PubMedCrossRef
33.
Papadimas J, Goulis DG, Giannouli C, Papanicolaou A, Tarlatzis B, Bontis JN. Ambiguous genitalia, 45, x/46, xy mosaic karyotype, and y chromosome microdeletions in a 17-year-old man. Fertil Steril. 2001;76:1261–3.PubMedCrossRef
34.
Rosa RF, D’Ecclesiis WF, Dibbi RP, Rosa RC, Trevisan P, Graziadio C, et al. 45, x/46, xy mosaicism: report on 14 patients from a Brazilian hospital. A retrospective study. Sao Paulo medical journal. Rev Paul Med. 2014;132:332–8.
35.
Keymolen K, Van Berkel K, Vorsselmans A, Staessen C, Liebaers I. Pregnancy outcome in carriers of Robertsonian translocations. Am J Med Genet A. 2011;155A:2381–5.PubMedCrossRef
36.
Godo A, Blanco J, Vidal F, Sandalinas M, Garcia-Guixe E, Anton E. Altered segregation pattern and numerical chromosome abnormalities interrelate in spermatozoa from Robertsonian translocation carriers. Reprod Biomed Online. 2015;31:79–88.PubMedCrossRef
37.
Dana M, Stoian V. Association of pericentric inversion of chromosome 9 and infertility in Romanian population. Maedica. 2012;7:25–9.PubMedPubMedCentral
38.
Mozdarani H, Meybodi AM, Karimi H. Impact of pericentric inversion of chromosome 9 [inv (9) (p11q12)] on infertility. Indian J Hum Genet. 2007;13:26–9.PubMedPubMedCentralCrossRef
39.
Collodel G, Moretti E, Capitani S, Piomboni P, Anichini C, Estenoz M, et al. Tem, fish and molecular studies in infertile men with pericentric inversion of chromosome 9. Andrologia. 2006;38:122–7.PubMedCrossRef
40.
Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, et al. Human y chromosome azoospermia factors (AZF) mapped to different subregions in yq11. Hum Mol Genet. 1996;5:933–43.PubMedCrossRef
41.
Stahl PJ, Masson P, Mielnik A, Marean MB, Schlegel PN, Paduch DA. A decade of experience emphasizes that testing for y microdeletions is essential in American men with azoospermia and severe oligozoospermia. Fertil Steril. 2010;94:1753–6.PubMedCrossRef
42.
Navarro-Costa P. Sex, rebellion and decadence: the scandalous evolutionary history of the human y chromosome. Biochim Biophys Acta. 1822;2012:1851–63.
43.
Sen S, Pasi AR, Dada R, Shamsi MB, Modi D. Y chromosome microdeletions in infertile men: prevalence, phenotypes and screening markers for the Indian population. J Assist Reprod Genet. 2013;30:413–22.PubMedPubMedCentralCrossRef
44.
Hopps CV, Mielnik A, Goldstein M, Palermo GD, Rosenwaks Z, Schlegel PN. Detection of sperm in men with y chromosome microdeletions of the AZFA, AZFB and AZFC regions. Hum Reprod. 2003;18:1660–5.PubMedCrossRef
45.
Asero P, Calogero AE, Condorelli RA, Mongioi L, Vicari E, Lanzafame F, et al. Relevance of genetic investigation in male infertility. J Endocrinol Investig. 2014;37:415–27.CrossRef
46.
Saxena R, de Vries JW, Repping S, Alagappan RK, Skaletsky H, Brown LG, et al. Four daz genes in two clusters found in the AZFC region of the human y chromosome. Genomics. 2000;67:256–67.PubMedCrossRef
47.
Kuroda-Kawaguchi T, Skaletsky H, Brown LG, Minx PJ, Cordum HS, Waterston RH, et al. The AZFC region of the y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet. 2001;29:279–86.PubMedCrossRef
48.
Noordam MJ, van Daalen SK, Hovingh SE, Korver CM, van der Veen F, Repping S. A novel partial deletion of the y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts. Hum Reprod. 2011;26:713–23.PubMedCrossRef
49.
Patsalis PC, Sismani C, Quintana-Murci L, Taleb-Bekkouche F, Krausz C, McElreavey K. Effects of transmission of y chromosome azfc deletions. Lancet (London, England). 2002;360:1222–4.CrossRef
50.
Repping S, Skaletsky H, Lange J, Silber S, Van Der Veen F, Oates RD, et al. Recombination between palindromes p5 and p1 on the human y chromosome causes massive deletions and spermatogenic failure. Am J Hum Genet. 2002;71:906–22.PubMedPubMedCentralCrossRef
51.
Ferlin A, Arredi B, Speltra E, Cazzadore C, Selice R, Garolla A, et al. Molecular and clinical characterization of y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab. 2007;92:762–70.PubMedCrossRef
52.
Ramathal C, Angulo B, Sukhwani M, Cui J, Durruthy-Durruthy J, Fang F, et al. DDX3Y gene rescue of a y chromosome AZFa deletion restores germ cell formation and transcriptional programs. Sci Rep. 2015;5:15041.PubMedPubMedCentralCrossRef
53.
Foresta C, Moro E, Rossi A, Rossato M, Garolla A, Ferlin A. Role of the AZFa candidate genes in male infertility. J Endocrinol Investig. 2000;23:646–51.CrossRef
54.
Blanco P, Shlumukova M, Sargent CA, Jobling MA, Affara N, Hurles ME. Divergent outcomes of intrachromosomal recombination on the human y chromosome: male infertility and recurrent polymorphism. J Med Genet. 2000;37:752–8.PubMedPubMedCentralCrossRef
55.
Schultz N, Hamra FK, Garbers DL. A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proc Natl Acad Sci U S A. 2003;100:12201–6.PubMedPubMedCentralCrossRef
56.
Aston KI. Genetic susceptibility to male infertility: news from genome-wide association studies. Andrology. 2014;2:315–21.PubMedCrossRef
57.
Pankow S, Bamberger C, Calzolari D, Martinez-Bartolome S, Lavallee-Adam M, Balch WE, et al. F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature. 2015;528:510–6.PubMedPubMedCentralCrossRef
58.
Sharma H, Mavuduru RS, Singh SK, Prasad R. Increased frequency of CFTR gene mutations identified in Indian infertile men with non-CBAVD obstructive azoospermia and spermatogenic failure. Gene. 2014;548:43–7.PubMedCrossRef
59.
Castellani C, Picci L, Tamanini A, Girardi P, Rizzotti P, Assael BM. Association between carrier screening and incidence of cystic fibrosis. JAMA. 2009;302:2573–9.PubMedCrossRef
60.
Yu J, Chen Z, Ni Y, Li Z. Cftr mutations in men with congenital bilateral absence of the vas deferens (cbavd): a systemic review and meta-analysis. Hum Reprod (Oxford, England). 2012;27:25–35.CrossRef
61.
Schlegel PN, Shin D, Goldstein M. Urogenital anomalies in men with congenital absence of the vas deferens. J Urol. 1996;155:1644–8.PubMedCrossRef
62.
Goldstein M, Schlossberg S. Men with congenital absence of the vas deferens often have seminal vesicles. J Urol. 1988;140:85–6.PubMed
63.
Giuliani R, Antonucci I, Torrente I, Grammatico P, Palka G, Stuppia L. Identification of the second CFTR mutation in patients with congenital bilateral absence of vas deferens undergoing ART protocols. Asian J Androl. 2010;12:819–26.PubMedPubMedCentralCrossRef
64.
Patrizio P, Zielenski J. Congenital absence of the vas deferens: a mild form of cystic fibrosis. Mol Med Today. 1996;2:24–31.PubMedCrossRef
65.
SM B, LM T. The reproductive sustem. In: LM T, editor. Cystic fibrosis. New York: Thieme-Stratton, Inc; 1987.
66.
Chen H, Ruan YC, Xu WM, Chen J, Chan HC. Regulation of male fertility by CFTR and implications in male infertility. Hum Reprod Update. 2012;18:703–13.PubMedCrossRef
67.
Mocanu E, Shattock R, Barton D, Rogers M, Conroy R, Sheils O, et al. All azoospermic males should be screened for cystic fibrosis mutations before intracytoplasmic sperm injection. Fertil Steril. 2010;94:2448–50.PubMedCrossRef
68.
Ravnik-Glavac M, Svetina N, Zorn B, Peterlin B, Glavac D. Involvement of CFTR gene alterations in obstructive and nonobstructive infertility in men. Genet Test. 2001;5:243–7.PubMedCrossRef
69.
Schlegel PN, Cohen J, Goldstein M, Alikani M, Adler A, Gilbert BR, et al. Cystic fibrosis gene mutations do not affect sperm function during in vitro fertilization with micromanipulation for men with bilateral congenital absence of vas deferens. Fertil Steril. 1995;64:421–6.PubMedCrossRef
70.
Yu J, Chen Z, Zhang T, Li Z, Ni Y, Li Z. Association of genetic variants in CFTR gene, ivs8 c.1210-12t[5_9] and c.1210-35_1210-12gt[8_12], with spermatogenetic failure: case-control study and meta-analysis. Mol Hum Reprod. 2011;17:594–603.PubMedCrossRef
71.
Elhanbly S, El-Saied MA, Fawzy M, El-Refaeey A, Mostafa T. Relationship of paternal age with outcome of percutaneous epididymal sperm aspiration-intracytoplasmic sperm injection, in cases of congenital bilateral absence of the vas deferens. Fertil Steril. 2015;104:602–6.PubMedCrossRef
72.
Llabador MA, Pagin A, Lefebvre-Maunoury C, Marcelli F, Leroy-Martin B, Rigot JM, et al. Congenital bilateral absence of the vas deferens: the impact of spermatogenesis quality on intracytoplasmic sperm injection outcomes in 108 men. Andrology. 2015;3:473–80.PubMedCrossRef
73.
Entrala-Bernal C, Montes-Castillo C, Alvarez-Cubero MJ, Gutierrez-Alcantara C, Fernandez-Rosado F, Martinez-Espiotan E, et al. Genetic diagnosis of idiopathic hypogonadotrophic hypogonadism: a new point mutation in the kal2 gene. Hormones (Athens, Greece). 2014;13:280–5.
74.
Dode C, Levilliers J, Dupont JM, De Paepe A, Le Du N, Soussi-Yanicostas N, et al. Loss-of-function mutations in fgfr1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003;33:463–5.PubMedCrossRef
75.
Della Valle E, Vezzani S, Rochira V, Granata ARM, Madeo B, Genovese E, et al. Prevalence of olfactory and other developmental anomalies in patients with central hypogonadotropic hypogonadism. Front Endocrinol. 2013;4:70.CrossRef
76.
Mitchell AL, Dwyer A, Pitteloud N, Quinton R. Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory. Trends Endocrinol Metab. 2011;22:249–58.PubMed
77.
de Castro F, Esteban PF, Bribian A, Murcia-Belmonte V, Garcia-Gonzalez D, Clemente D. The adhesion molecule anosmin-1 in neurology: Kallmann syndrome and beyond. Adv Neurobiol. 2014;8:273–92.PubMedCrossRef
78.
Sarfati J, Bouvattier C, Bry-Gauillard H, Cartes A, Bouligand J, Young J. Kallmann syndrome with fgfr1 and kal1 mutations detected during fetal life. Orphanet J Rare Dis. 2015;10:71.PubMedPubMedCentralCrossRef
79.
Quinton R, Duke VM, Robertson A, Kirk JMW, Matfin G, De Zoysa PA, Azcona C, MacColl GS, Jacobs HS, Conway GS, Besser M, Stanhope RG, Bouloux P-MG: Idiopathic gonadotrophin deficiency: genetic questions addressed through phenotypic characterization.
80.
Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, Minowada S, Shimotsuka A, Shishiba Y, Yokozawa M, Yasuda T, Nagasaki K, Hasegawa D, Hasegawa Y, Tachibana K, Naiki Y, Horikawa R, Tanaka T, Ogata T.
81.
Oliveira LMB, Seminara SB, Beranova M, Hayes FJ, Valkenburgh SB, Schipani E, Costa EMF, Latronico AC, Crowley WF, Vallejo M.
82.
Hu Y, Bouloux PM. Novel insights in fgfr1 regulation: lessons from Kallmann syndrome. Trends Endocrinol Metab. 2010;21:385–93.PubMedCrossRef
83.
Villanueva C, Jacobson-Dickman E, Xu C, Manouvrier S, Dwyer AA, Sykiotis GP, et al. Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of fgfr1 mutations. Genet Med. 2015;17:651–9.PubMedCrossRef
84.
Zhang S, Wang T, Yang J, Liu Z, Wang S, Liu J. A fertile male patient with Kallmann syndrome and two missense mutations in the kal1 gene. Fertil Steril. 1789;2011(95):e1783–6.
85.
Boehm U, Bouloux PM, Dattani MT, de Roux N, Dode C, Dunkel L, et al. Expert consensus document: European consensus statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11:547–64.PubMed
86.
87.
Wang PJ, McCarrey JR, Yang F, Page DC. An abundance of x-linked genes expressed in spermatogonia. Nat Genet. 2001;27:422–6.PubMedCrossRef
88.
Yang F, Gell K, van der Heijden GW, Eckardt S, Leu NA, Page DC, et al. Meiotic failure in male mice lacking an x-linked factor. Genes Dev. 2008;22:682–91.PubMedPubMedCentralCrossRef
89.
Adelman CA, Petrini JH. Zip4h (tex11) deficiency in the mouse impairs meiotic double strand break repair and the regulation of crossing over. PLoS Genet. 2008;4:e1000042.PubMedPubMedCentralCrossRef
90.
Yang F, Silber S, Leu NA, Oates RD, Marszalek JD, Skaletsky H, et al. Tex11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse. EMBO Mol Med. 2015;7:1198–210.PubMedPubMedCentralCrossRef
91.
Yatsenko AN, Georgiadis AP, Ropke A, Berman AJ, Jaffe T, Olszewska M, et al. X-linked tex11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med. 2015;372:2097–107.PubMedPubMedCentralCrossRef
92.
Alvarez Sedo C, Rawe VY, Chemes HE. Acrosomal biogenesis in human globozoospermia: immunocytochemical, ultrastructural and proteomic studies. Hum Reprod (Oxford, England). 2012;27:1912–21.CrossRef
93.
Pierre V, Martinez G, Coutton C, Delaroche J, Yassine S, Novella C, et al. Absence of dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus. Dev (Cambridge, England). 2012;139:2955–65.CrossRef
94.
Koscinski I, Elinati E, Fossard C, Redin C, Muller J, Velez de la Calle J, et al. Dpy19l2 deletion as a major cause of globozoospermia. Am J Hum Genet. 2011;88:344–50.PubMedPubMedCentralCrossRef
95.
Kuentz P, Vanden Meerschaut F, Elinati E, Nasr-Esfahani MH, Gurgan T, Iqbal N, et al. Assisted oocyte activation overcomes fertilization failure in globozoospermic patients regardless of the dpy19l2 status. Hum Reprod. 2013;28:1054–61.PubMedCrossRef
96.
Ghedir H, Ibala-Romdhane S, Okutman O, Viot G, Saad A, Viville S. Identification of a new dpy19l2 mutation and a better definition of dpy19l2 deletion breakpoints leading to globozoospermia. Mol Hum Reprod. 2016;22:35–45.PubMedCrossRef
97.
Dada R, Kumar M, Jesudasan R, Fernandez JL, Gosalvez J, Agarwal A. Epigenetics and its role in male infertility. J Assist Reprod Genet. 2012;29:213–23.PubMedPubMedCentralCrossRef
98.
99.
100.
Odom LN, Segars J. Imprinting disorders and assisted reproductive technology. Curr Opin Endocrinol, Diabetes Obes. 2010;17:517–22.CrossRef
101.
Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308:1466–9.PubMedCrossRef
102.
Donkin IVS, Ingerslev LR, Qian K, Mechta M, Nordkap L, Mortensen B, et al. Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metab. 2016;23:1–10.CrossRef
103.
Stuppia L, Franzago M, Ballerini P, Gatta V, Antonucci I. Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health. Clin Epigenetics. 2015;7:120.PubMedPubMedCentralCrossRef
104.
105.
Li E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet. 2002;3:662–73.PubMedCrossRef
106.
Houshdaran S, Cortessis VK, Siegmund K, Yang A, Laird PW, Sokol RZ. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS One. 2007;2:e1289.PubMedPubMedCentralCrossRef
107.
Benchaib M, Braun V, Ressnikof D, Lornage J, Durand P, Niveleau A, et al. Influence of global sperm DNA methylation on ivf results. Hum Reprod. 2005;20:768–73.PubMedCrossRef
108.
Montjean D, Zini A, Ravel C, Belloc S, Dalleac A, Copin H, et al. Sperm global DNA methylation level: association with semen parameters and genome integrity. Andrology. 2015;3:235–40.PubMedCrossRef
109.
Jenkins TG, Carrell DT. The sperm epigenome and potential implications for the developing embryo. Reproduction (Cambridge, England). 2012;143:727–34.CrossRef
110.••
Gunes S, Arslan MA, Hekim GN, Asci R: The role of epigenetics in idiopathic male infertility. Journal of assisted reproduction and genetics 2016. Review article with detailed explanation about epigenetic aspects of male infertility.
111.
Jenkins TG, Aston KI, Meyer TD, Hotaling JM, Shamsi MB, Johnstone EB, et al. Decreased fecundity and sperm DNA methylation patterns. Fertil Steril. 2016;105:51–7. e53.PubMedCrossRef
112.
Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S. Molecular basis for the discrimination of repressive methyl-lysine marks in histone h3 by polycomb and hp1 chromodomains. Genes Dev. 2003;17:1870–81.PubMedPubMedCentralCrossRef
113.
114.
Vigodner M, Ishikawa T, Schlegel PN, Morris PL. Sumo-1, human male germ cell development, and the androgen receptor in the testis of men with normal and abnormal spermatogenesis. Am J Physiol Endocrinol Metab. 2006;290:E1022–33.PubMedCrossRef
115.
Yuen BT, Bush KM, Barrilleaux BL, Cotterman R, Knoepfler PS. Histone h3.3 regulates dynamic chromatin states during spermatogenesis. Dev (Cambridge, England. 2014;141:3483–94.CrossRef
116.
La Spina FA, Romanato M, Brugo-Olmedo S, De Vincentiis S, Julianelli V, Rivera RM, et al. Heterogeneous distribution of histone methylation in mature human sperm. J Assist Reprod Genet. 2014;31:45–9.PubMedCrossRef
117.
Hammoud SS, Nix DA, Hammoud AO, Gibson M, Cairns BR, Carrell DT. Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum Reprod (Oxford, England). 2011;26:2558–69.CrossRef
118.
Havas K, Flaus A, Phelan M, Kingston R, Wade PA, Lilley DM, et al. Generation of superhelical torsion by ATP-dependent chromatin remodeling activities. Cell. 2000;103:1133–42.PubMedCrossRef
119.
Kingston RE, Narlikar GJ. Atp-dependent remodeling and acetylation as regulators of chromatin fluidity. Genes Dev. 1999;13:2339–52.PubMedCrossRef
120.
Conwell CC, Vilfan ID, Hud NV. Controlling the size of nanoscale toroidal DNA condensates with static curvature and ionic strength. Proc Natl Acad Sci U S A. 2003;100:9296–301.PubMedPubMedCentralCrossRef
121.
Zhang X, San Gabriel M, Zini A. Sperm nuclear histone to protamine ratio in fertile and infertile men: evidence of heterogeneous subpopulations of spermatozoa in the ejaculate. J Androl. 2006;27:414–20.PubMedCrossRef
122.
Sonnack V, Failing K, Bergmann M, Steger K. Expression of hyperacetylated histone h4 during normal and impaired human spermatogenesis. Andrologia. 2002;34:384–90.PubMedCrossRef
123.
Steger K, Failing K, Klonisch T, Behre HM, Manning M, Weidner W, et al. Round spermatids from infertile men exhibit decreased protamine-1 and -2 mRNA. Hum Reprod. 2001;16:709–16.PubMedCrossRef
124.
125.
Nanassy L, Carrell DT. Abnormal methylation of the promoter of crem is broadly associated with male factor infertility and poor sperm quality but is improved in sperm selected by density gradient centrifugation. Fertil Steril. 2011;95:2310–4.PubMedCrossRef
126.
Rogenhofer N, Dansranjavin T, Schorsch M, Spiess A, Wang H, von Schonfeldt V, et al. The sperm protamine mRNA ratio as a clinical parameter to estimate the fertilizing potential of men taking part in an ART programme. Hum Reprod (Oxford, England). 2013;28:969–78.CrossRef
127.
Hamad MF, Shelko N, Kartarius S, Montenarh M, Hammadeh ME. Impact of cigarette smoking on histone (h2b) to protamine ratio in human spermatozoa and its relation to sperm parameters. Andrology. 2014;2:666–77.PubMedCrossRef
128.
Ni K, Steger K, Yang H, Wang H, Hu K, Chen B. Sperm protamine mRNA ratio and DNA fragmentation index represent reliable clinical biomarkers for men with varicocele after microsurgical varicocele ligation. J Urol. 2014;192:170–6.PubMedCrossRef
129.
130.
Lee RC, Feinbaum RL, Ambros V. The c. Elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.PubMedCrossRef
131.
132.
Wu W, Hu Z, Qin Y, Dong J, Dai J, Lu C, et al. Seminal plasma microRNAs: potential biomarkers for spermatogenesis status. Mol Hum Reprod. 2012;18:489–97.PubMedCrossRef
133.
Lian J, Zhang X, Tian H, Liang N, Wang Y, Liang C, et al. Altered microRNA expression in patients with non-obstructive azoospermia. Reprod Biol Endocrinol. 2009;7:13.PubMedPubMedCentralCrossRef
134.
Papaioannou MD, Nef S. MicroRNAs in the testis: building up male fertility. J Androl. 2010;31:26–33.PubMedCrossRef
135.
136.
Salas-Huetos A, Blanco J, Vidal F, Mercader JM, Garrido N, Anton E. New insights into the expression profile and function of micro-ribonucleic acid in human spermatozoa. Fertil Steril. 2014;102:213–22. e214.PubMedCrossRef
137.
Kozomara A, Griffiths-Jones S. Mirbase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014;42:D68–73.PubMedCrossRef
138.
Gonzalez-Marin C, Gosalvez J, Roy R. Types, causes, detection and repair of DNA fragmentation in animal and human sperm cells. Int J Mol Sci. 2012;13:14026–52.PubMedPubMedCentralCrossRef
139.
Aitken RJ, De Iuliis GN. On the possible origins of DNA damage in human spermatozoa. Mol Hum Reprod. 2010;16:3–13.PubMedCrossRef
140.
Greco E, Scarselli F, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, et al. Efficient treatment of infertility due to sperm DNA damage by icsi with testicular spermatozoa. Hum Reprod (Oxford, England). 2005;20:226–30.CrossRef
141.
Neto FT, Bach PV, Najari BB, Li PS, Goldstein M: Spermatogenesis in humans and its affecting factors. Semin Cell Dev Biol 2016.
142.
Aitken RJ, Koppers AJ. Apoptosis and DNA damage in human spermatozoa. Asian J Androl. 2011;13:36–42.PubMedCrossRef
143.
Spano M, Bonde JP, Hjollund HI, Kolstad HA, Cordelli E, Leter G. Sperm chromatin damage impairs human fertility. The Danish first pregnancy planner study team. Fertil Steril. 2000;73:43–50.PubMedCrossRef
144.
Zidi-Jrah I, Hajlaoui A, Mougou-Zerelli S, Kammoun M, Meniaoui I, Sallem A, et al. Relationship between sperm aneuploidy, sperm DNA integrity, chromatin packaging, traditional semen parameters, and recurrent pregnancy loss. Fertil Steril. 2016;105:58–64.PubMedCrossRef
145.•
Osman A, Alsomait H, Seshadri S, El-Toukhy T, Khalaf Y. The effect of sperm DNA fragmentation on live birth rate after ivf or icsi: a systematic review and meta-analysis. Reprod Biomed Online. 2015;30:120–7. Meta-analysis showing the impact of sperm DNA fragmentation in IVF and ICSI outcomes. IVF outcomes seem to be more affected than ICSI outcomes by high levels of sperm DNA fragmentation.PubMedCrossRef
146.
Esteves SC, Sanchez-Martin F, Sanchez-Martin P, Schneider DT, Gosalvez J. Comparison of reproductive outcome in oligozoospermic men with high sperm DNA fragmentation undergoing intracytoplasmic sperm injection with ejaculated and testicular sperm. Fertil Steril. 2015;104:1398–405.PubMedCrossRef
147.
Evgeni E, Charalabopoulos K, Asimakopoulos B. Human sperm DNA fragmentation and its correlation with conventional semen parameters. J Reprod Infertility. 2014;15:2–14.
148.
O’Flynn O’Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril. 2010;93:1–12.PubMedCrossRef
149.
Abu-Halima M, Hammadeh M, Backes C, Fischer U, Leidinger P, Lubbad AM, et al. Panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility. Fertil Steril. 2014;102:989–97. e981.PubMedCrossRef
150.
Wang C, Yang C, Chen X, Yao B, Yang C, Zhu C, et al. Altered profile of seminal plasma microRNAs in the molecular diagnosis of male infertility. Clin Chem. 2011;57:1722–31.PubMedCrossRef
151.
Wu W, Qin Y, Li Z, Dong J, Dai J, Lu C, et al. Genome-wide microRNA expression profiling in idiopathic non-obstructive azoospermia: significant up-regulation of mir-141, mir-429 and mir-7-1-3p. Hum Reprod. 2013;28:1827–36.PubMedCrossRef
152.
Dabaja AA, Mielnik A, Robinson BD, Wosnitzer MS, Schlegel PN, Paduch DA. Possible germ cell-sertoli cell interactions are critical for establishing appropriate expression levels for the sertoli cell-specific microRNA, mir-202-5p, in human testis. Basic Clin Androl. 2015;25:2.PubMedPubMedCentralCrossRef
Metadata
Title
Genetics of Male Infertility
Authors
Filipe Tenorio Lira Neto
Phil Vu Bach
Bobby Baback Najari
Philip Shihua Li
Marc Goldstein
Publication date
01-10-2016
Publisher
Springer US
Published in
Current Urology Reports / Issue 10/2016
Print ISSN: 1527-2737
Electronic ISSN: 1534-6285
DOI
https://doi.org/10.1007/s11934-016-0627-x

Other articles of this Issue 10/2016

Current Urology Reports 10/2016 Go to the issue

Men’s Health (A Dabaja, Section Editor)

Transitional Urology for Male Adolescents: What Adult Urologists Should Know

Men’s Health (A Dabaja, Section Editor)

Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review

Men’s Health (A Dabaja, Section Editor)

Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health

Case Report

Challenging Case: Stones

New Imaging Techniques (A Rastinehad and S Rais-Bahrami, Section Editors)

Targeted Anterior Gland Focal Therapy—a Novel Treatment Option for a Better Defined Disease

Case Report

Nocturia