Men's Reproductive and Sexual Health Throughout the Lifespan An Integrated Approach to Fertility, Sexual Function, and Vitality
Book contents
- Men’s Reproductive and Sexual Health throughout the Lifespan
- Men’s Reproductive and Sexual Health throughout the Lifespan
- Copyright page
- Contents
- Contributors
- Preface
- Section 1 An Introduction to Men’s Health Care
- Section 2 The Biology of Male Reproduction and Infertility
- Chapter 4 Current Understanding of the Physiology and Histology of Human Spermatogenesis
- Chapter 5 Male Reproductive Endocrinology
- Chapter 6 Sperm Chromatin Packaging and the Toroid Linker Model
- Chapter 7 Ejaculation and Sperm Transport
- Chapter 8 Genetic Aspects of Male Infertility
- Chapter 9 The Mechanistic and Predictive Utility of Sperm Epigenetics
- Chapter 10 Aging and Environmental Interactions with the Sperm Epigenome
- Chapter 11 The Effects of Aging on Male Fertility and the Health of Offspring
- Section 3 Clinical Evaluation and Treatment of Male Infertility
- Section 4 Laboratory Evaluation and Treatment of Male Infertility
- Section 5 Medical and Surgical Management of Issues of Male Health
- Index
- References
Chapter 8 - Genetic Aspects of Male Infertility
from Section 2 - The Biology of Male Reproduction and Infertility
Published online by Cambridge University Press: 06 December 2023
Book contents
- Men’s Reproductive and Sexual Health throughout the Lifespan
- Men’s Reproductive and Sexual Health throughout the Lifespan
- Copyright page
- Contents
- Contributors
- Preface
- Section 1 An Introduction to Men’s Health Care
- Section 2 The Biology of Male Reproduction and Infertility
- Chapter 4 Current Understanding of the Physiology and Histology of Human Spermatogenesis
- Chapter 5 Male Reproductive Endocrinology
- Chapter 6 Sperm Chromatin Packaging and the Toroid Linker Model
- Chapter 7 Ejaculation and Sperm Transport
- Chapter 8 Genetic Aspects of Male Infertility
- Chapter 9 The Mechanistic and Predictive Utility of Sperm Epigenetics
- Chapter 10 Aging and Environmental Interactions with the Sperm Epigenome
- Chapter 11 The Effects of Aging on Male Fertility and the Health of Offspring
- Section 3 Clinical Evaluation and Treatment of Male Infertility
- Section 4 Laboratory Evaluation and Treatment of Male Infertility
- Section 5 Medical and Surgical Management of Issues of Male Health
- Index
- References
Summary
Approximately one out of every 15 men will exhibit subfertility or infertility, and some data suggest the incidence of male infertility is increasing. While a number of factors can cause male infertility, there is strong and growing evidence that genetic factors contribute to a significant proportion of cases. Several significant genetic factors have long been recognized as clinically relevant causes of male infertility including Klinefelter syndrome, microdeletions of the Y chromosome, and cystic fibrosis transmembrane conductance regulator mutations. Since the discovery of these factors in the 1950s, 1970s, and 1980s respectively, there has been a relative dearth in the discovery of additional clinically relevant genetic factors underlying male infertility until recently. However, with the application of emerging genome-wide genetic approaches, along with the collaborative efforts from a growing number of groups, male infertility genetics has experienced a renaissance of sorts in the past decade with significant new discoveries being reported frequently over recent years. This chapter will briefly review the history of male infertility genetics as well as some of the more recent discoveries and efforts beyond gene screening approaches that have and will continue to advance the field.
Keywords
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- Chapter
- Information
- Men's Reproductive and Sexual Health Throughout the LifespanAn Integrated Approach to Fertility, Sexual Function, and Vitality, pp. 67 - 75Publisher: Cambridge University PressPrint publication year: 2023
References
Krausz, C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab. 2011;25:271–285.Google Scholar
Watson, JD, Crick, FH. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature. 1953;171:737–738.Google Scholar
Jacobs, PA, Strong, JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature. 1959;183:302–303.CrossRefGoogle ScholarPubMed
Lander, ES, Linton, LM, Birren, B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.Google Scholar
Tiepolo, L, Zuffardi, O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet. 1976;34:119–124.CrossRefGoogle ScholarPubMed
Chillon, M, Casals, T, Mercier, B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med. 1995;332:1475–1480.CrossRefGoogle ScholarPubMed
Aston, KI. Genetic susceptibility to male infertility: news from genome-wide association studies. Andrology. 2014;2:315–321.Google Scholar
Tuttelmann, F, Rajpert-De Meyts, E, Nieschlag, E, Simoni, M. Gene polymorphisms and male infertility – a meta-analysis and literature review. Reprod Biomed Online. 2007;15:643–658.CrossRefGoogle ScholarPubMed
Aston, KI, Carrell, DT. Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. J Androl. 2009;30:711–725.CrossRefGoogle ScholarPubMed
Aston, KI, Conrad, DF. A review of genome-wide approaches to study the genetic basis for spermatogenic defects. Methods Mol Biol. 2013;927:397–410.CrossRefGoogle Scholar
Fruhmesser, A, Vogt, PH, Zimmer, J, et al. (2013) Single nucleotide polymorphism array analysis in men with idiopathic azoospermia or oligoasthenozoospermia syndrome. Fertil Steril. 100:81–87.CrossRefGoogle ScholarPubMed
Hu, Z, Xia, Y, Guo, X, et al. A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia. Nature Genetics. 2012;44:183–186.Google Scholar
Krausz, C, Giachini, C, Lo Giacco, D, et al. High resolution X chromosome-specific array-CGH detects new CNVs in infertile males. PLoS ONE. 2012;7:e44887.Google Scholar
Stouffs, K, Vandermaelen, D, Massart, A, et al. Array comparative genomic hybridization in male infertility. Hum Reprod. 2012;27:921–929.Google Scholar
Dam, AH, Koscinski, I, Kremer, JA, et al. Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. Am J Hum Genet. 2007;81:813–820.CrossRefGoogle ScholarPubMed
Koscinski, I, Elinati, E, Fossard, C, et al. DPY19L2 deletion as a major cause of globozoospermia. Am J Hum Gen. 2011;88:344–350.Google Scholar
Lopes, AM, Aston, KI, Thompson, E, et al. Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1. PLoS Genetics. 2013;9:e1003349.CrossRefGoogle ScholarPubMed
Yatsenko, AN, Georgiadis, AP, Ropke, A, et al. X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med. 2015;372:2097–2107.Google Scholar
Oud, MS, Volozonoka, L, Smits, RM, Vissers, L, Ramos, L, Veltman, JA. A systematic review and standardized clinical validity assessment of male infertility genes. Hum Reprod. 2019;34:932–941.Google Scholar
Delot, EC, Papp, JC, DSD-TRN Genetics Workgroup, Sandberg, DE, Vilain, E. Genetics of disorders of sex development: the DSD-TRN experience. Endocrinol Metab Clin North Am. 2017;46:519–537.CrossRefGoogle ScholarPubMed
Bianco, SD, Kaiser, UB. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol. 2009;5:569–576.CrossRefGoogle ScholarPubMed
Eggers, S, Sadedin, S, van den Bergen, JA, et al. Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biol. 2016;17:243.Google Scholar
Boehm, U, Bouloux, PM, Dattani, MT, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism – pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11:547–564.Google Scholar
Jarow, JP, Espeland, MA, Lipshultz, LI Evaluation of the azoospermic patient. J Urol. 1989;142:62–65.Google Scholar
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. 2012;27:25–35.Google Scholar
Patat, O, Pagin, A, Siegfried, A, et al. Truncating mutations in the adhesion G protein-coupled receptor G2 gene ADGRG2 cause an X-linked congenital bilateral absence of vas deferens. Am J Hum Genet. 2016;99:437–442.Google Scholar
Yang, B, Wang, J, Zhang, W, et al. Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population. Andrology. 2017;5:954–957.Google Scholar
Kasak, L, Laan, M. Monogenic causes of non-obstructive azoospermia: challenges, established knowledge, limitations and perspectives. Hum Genet. 2021;140:135–154.Google Scholar
Vockel, M, Riera-Escamilla, A, Tuttelmann, F, Krausz, C. The X chromosome and male infertility. Hum Genet. 2021;140:203–215.CrossRefGoogle ScholarPubMed
Punab, M, Poolamets, O, Paju, P, et al. Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod. 2017;32:18–31.Google Scholar
Krausz, C, Riera-Escamilla, A. Genetics of male infertility. Nat Rev Urol. 2018;15:369–384.Google Scholar
Tuttelmann, F, Simoni, M, Kliesch, S, et al. Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PLoS ONE. 2011;6:e19426.Google Scholar
Kasak, L, Punab, M, Nagirnaja, L, et al. Bi-allelic recessive loss-of-function variants in FANCM cause non-obstructive azoospermia. Am J Hum Genet. 2018;103:200–212.Google Scholar
Krausz, C, Riera-Escamilla, A, Chianese, C, et al. From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia. Genet Med. 2019;21:189–194.Google Scholar
Wyrwoll, MJ, Temel, SG, Nagirnaja, L, et al. Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility. Am J Hum Genet. 2020;107:342–351.Google Scholar
Dam, AH, Feenstra, I, Westphal, JR. Ramos, L, van Golde, RJ, Kremer, JA. Globozoospermia revisited. Hum Reprod Update. 2007;13:63–75.Google Scholar
Harbuz, R, Zouari, R, Pierre, V, et al. A recurrent deletion of DPY19L2 causes infertility in man by blocking sperm head elongation and acrosome formation. Am J Hum Genet. 2011;88:351–361.CrossRefGoogle Scholar
Amiri-Yekta, A, Coutton, C, Kherraf, ZE, et al. Whole-exome sequencing of familial cases of multiple morphological abnormalities of the sperm flagella (MMAF) reveals new DNAH1 mutations. Hum Reprod. 2016;31:2872–2880.Google Scholar
Sha, YW, Wang, X, Xu, X, et al. Novel mutations in CFAP44 and CFAP43 cause multiple morphological abnormalities of the sperm flagella (MMAF). Reprod Sci. 2017:1933719117749756.Google Scholar
Wang, WL, Tu, CF, Tan, YQ. Insight on multiple morphological abnormalities of sperm flagella in male infertility: what is new? Asian J Androl. 2020;22:236–245.Google Scholar
Jung, M, Wells, D, Rusch, J, et al. Unified single-cell analysis of testis gene regulation and pathology in five mouse strains. Elife. 2019;8.CrossRefGoogle ScholarPubMed
Guo, J, Grow, EJ, Mlcochova, H, et al. The adult human testis transcriptional cell atlas. Cell Res. 2018;28:1141–1157.Google Scholar
Grabowski, P, Rappsilber, J. A primer on data analytics in functional genomics: how to move from data to insight? Trends Biochem Sci. 2019;44:21–32.CrossRefGoogle ScholarPubMed
Langmead, B, Nellore, A. Cloud computing for genomic data analysis and collaboration. Nat Rev Genet. 2018;19:208–219.Google Scholar
Wilfert, AB, Chao, KR, Kaushal, M, et al. Genome-wide significance testing of variation from single case exomes. Nat Genet. 2016;48:1455–1461.CrossRefGoogle ScholarPubMed
Komeya, M, Sato, T, Ogawa, T. In vitro spermatogenesis: a century-long research journey, still half way around. Reprod Med Biol. 2018;17:407–420.Google Scholar
Ibtisham, F, Wu, J, Xiao, M, et al. Progress and future prospect of in vitro spermatogenesis. Oncotarget. 2017;8:66709–66727.Google Scholar
Sato, T, Katagiri, K, Gohbara, A, et al. In vitro production of functional sperm in cultured neonatal mouse testes. Nature. 2011;471:504–507.Google Scholar
Coutton, C, Vargas, AS, Amiri-Yekta, A, et al. Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human. Nat Commun. 2018;9:686.CrossRefGoogle ScholarPubMed
Duquesnoy, P, Escudier, E, Vincensini, L, et al. Loss-of-function mutations in the human ortholog of Chlamydomonas reinhardtii ODA7 disrupt dynein arm assembly and cause primary ciliary dyskinesia. Am J Hum Genet. 2009;85:890–896.Google Scholar
Kherraf, ZE, Amiri-Yekta, A, Dacheux, D, et al. A homozygous ancestral SVA-insertion-mediated deletion in WDR66 induces multiple morphological abnormalities of the sperm flagellum and male infertility. Am J Hum Genet. 2018;103:400–412.Google Scholar
Yu, J, Wu, H, Wen, Y, et al. Identification of seven genes essential for male fertility through a genome-wide association study of non-obstructive azoospermia and RNA interference-mediated large-scale functional screening in Drosophila. Hum Mol Genet. 2015;24:1493–1503.CrossRefGoogle ScholarPubMed
Ramanagoudr-Bhojappa, R, Carrington, B, Ramaswami, M, et al. Multiplexed CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility. PLoS Genet. 2018;14:e1007821.Google Scholar
Jamsai, D, O’Bryan, MK. Mouse models in male fertility research. Asian J Androl. 2011;13:139–151.Google Scholar
Geister, KA, Timms, AE, Beier, DR. Optimizing genomic methods for mapping and identification of candidate variants in ENU mutagenesis screens using inbred mice. G3 (Bethesda). 2018;8:401–409.CrossRefGoogle ScholarPubMed
Kennedy, CL, O’Bryan, MK. N-ethyl-N-nitrosourea (ENU) mutagenesis and male fertility research. Hum Reprod Update. 2006;12:293–301.Google Scholar
De Jonge, C, Barratt, CLR. The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap. Andrology. 2019;7:762–768.CrossRefGoogle ScholarPubMed
Tuttelmann, F, Ruckert, C, Ropke, A. Disorders of spermatogenesis: perspectives for novel genetic diagnostics after 20 years of unchanged routine. Med Genet. 2018;30:12–20.Google Scholar
Smith, ED, Radtke, K, Rossi, M, et al. Classification of genes: standardized clinical validity assessment of gene-disease associations aids diagnostic exome analysis and reclassifications. Hum Mutat. 2017;38:600–608.Google Scholar
Strande, NT, Riggs, ER, Buchanan, AH, et al. Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the clinical genome resource. Am J Hum Genet. 2017;100:895–906.Google Scholar
Laan, M. Systematic review of the monogenetic causes of male infertility: the first step towards diagnostic gene panels in the andrology clinic. Hum Reprod. 2019;34:783–785.Google Scholar