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Chapter 4 - Current Understanding of the Physiology and Histology of Human Spermatogenesis

from Section 2 - The Biology of Male Reproduction and Infertility

Published online by Cambridge University Press:  06 December 2023

By
Chiara Capponi  and
Elena Vicini
Edited by
Douglas T. Carrell ,
Alexander W. Pastuszak  and
James M. Hotaling
Douglas T. Carrell
Affiliation:
Utah Center for Reproductive Medicine
Alexander W. Pastuszak
Affiliation:
University of Utah
James M. Hotaling
Affiliation:
Utah Center for Reproductive Medicine
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Summary

Spermatogenesis is a complex process that ensures daily production of mature male gametes. The differentiation of spermatogonia stem cells into spermatozoa requires the unfolding of several events that are highly regulated in time and space. During spermatogenesis, which takes place inside the seminiferous tubules, germ cells undergo profound morphological rearrangement as can be observed by classical histological analysis of human testis specimens. Spermatogenesis also brings about the dramatic rearrangement of genetic makeover of developing germ cells including homologous recombination and changes in the epigenetic landscape. In this chapter the different phases of human spermatogenesis and cell types involved are described with an emphasis on their morphological arrangements. In parallel, an update on novel findings concerning the cycle of the seminiferous epithelium, the kinetic of spermatogonial compartment, and the implications of single-cell transcriptome analysis of testicular cells will be provided.

Keywords

spermatogenesishumanspermatogonial stem cellsmale infertilitysingle cell RNA sequencing
Type
Chapter
Information
Men's Reproductive and Sexual Health Throughout the Lifespan
An Integrated Approach to Fertility, Sexual Function, and Vitality
 , pp. 23 - 33
Publisher: Cambridge University Press
Print publication year: 2023

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References

Soumillon, M, Necsulea, A, Weier, M, et al. Cellular source and mechanisms of high transcriptome complexity in the mammalian testis. Cell Rep. 2013;3(6):2179–2190.CrossRefGoogle ScholarPubMed
Uhlen, M, Fagerberg, L, Hallstrom, BM, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.CrossRefGoogle ScholarPubMed
Pineau, C, Hikmet, F, Zhang, C, et al. Cell type-specific expression of testis elevated genes based on transcriptomics and antibody-based proteomics. J Proteome Res. 2019;18(12):4215–4230.Google Scholar
Weinbauer, G, Luetjens, C, Simoni, M, Nieschlag, E. Physiology of testicular fuction. In: Nieschlag, E., Behre, HM, Nieschlag, S, eds. Andrology Male Reproductive Health and Dysfunction. 3rd ed. Springer-Verlag; 2010:11–59.Google Scholar
Petersen, PM, Seieroe, K, Pakkenberg, B. The total number of Leydig and Sertoli cells in the testes of men across various age groups: a stereological study. J Anat. 2015;226(2):175–179.Google Scholar
Ivell, R, Agoulnik, AI, Anand-Ivell, R. Relaxin-like peptides in male reproduction – a human perspective. Br J Pharmacol. 2017;174(10):990–1001.Google Scholar
Prince, FP. The human Leydig cell. In: Payne, AH, Hardy, MP, eds. The Leydig Cell in Health and Disease. Humana Press; 2007:71–89.Google Scholar
Chen, P, Zirkin, BR, Chen, H. Stem Leydig cells in the adult testis: characterization, regulation and potential applications. Endocrine Reviews. 41(1):22–32.Google Scholar
Head, JR, Neaves, WB, Billingham, RE. Immune privilege in the testis. I. Basic parameters of allograft survival. Transplantation. 1983;36(4):423–431.Google Scholar
Fijak, M, Pilatz, A, Hedger, MP, et al. Infectious, inflammatory and ‘autoimmune’ male factor infertility: how do rodent models inform clinical practice? Hum Reprod Update. 2018;24(4):416–441.Google Scholar
Maekawa, M, Kamimura, K, Nagano, T. Peritubular myoid cells in the testis: their structure and function. Arch Histol Cytol. 1996;59(1):1–13.CrossRefGoogle ScholarPubMed
Arenas, MI, Bethencourt, FR, Fraile, B, Paniagua, R. Immunocytochemical and quantitative study of the tunica albuginea testis in young and ageing men. Histochem Cell Biol. 1997;107(6):469–477.Google Scholar
Davidoff, MS, Breucker, H, Holstein, AF, Seidl, K. Cellular architecture of the lamina propria of human seminiferous tubules. Cell Tissue Res. 1990;262(2):253–261.CrossRefGoogle ScholarPubMed
Hargrove, JL, MacIndoe, JH, Ellis, LC. Testicular contractile cells and sperm transport. Fertil Steril. 1977;28(11):1146–1157.CrossRefGoogle ScholarPubMed
Mayerhofer, A. Human testicular peritubular cells: more than meets the eye. Reproduction. 2013;145(5):R107–R116.CrossRefGoogle ScholarPubMed
Volkmann, J, Muller, D, Feuerstacke, C, et al. Disturbed spermatogenesis associated with thickened lamina propria of seminiferous tubules is not caused by dedifferentiation of myofibroblasts. Hum Reprod. 2011;26(6):1450–1461.CrossRefGoogle Scholar
Sato, Y, Nozawa, S, Iwamoto, T. Study of spermatogenesis and thickening of lamina propria in the human seminiferous tubules. Fertil Steril. 2008;90(4):1310–1312.Google Scholar
Johnson, L, Zane, RS, Petty, CS, Neaves, WB. Quantification of the human Sertoli cell population: its distribution, relation to germ cell numbers, and age-related decline. Biol Reprod. 1984;31(4):785–795.Google Scholar
Franca, LR, Hess, RA, Dufour, JM, Hofmann, MC, Griswold, MD. The Sertoli cell: one hundred fifty years of beauty and plasticity. Andrology. 2016;4(2):189–212.Google Scholar
Setchell, BP. The secretion of fluid by the testes of rats, rams and goats with some observations on the effect of age, cryptorchidism and hypophysectomy. J Reprod Fertil. 1970;23(1):79–85.CrossRefGoogle ScholarPubMed
Stanton, PG. Regulation of the blood-testis barrier. Semin Cell Dev Biol. 2016;59:166–173.Google Scholar
Mruk, DD, Cheng, CY. The mammalian blood-testis barrier: its biology and regulation. Endocr Rev. 2015;36(5):564–591.Google Scholar
Makela, JA, Hobbs, RM. Molecular regulation of spermatogonial stem cell renewal and differentiation. Reproduction. 2019;158(5):R169–R187.Google Scholar
Santi, D, Crepieux, P, Reiter, E, et al. Follicle-stimulating hormone (FSH) action on spermatogenesis: a focus on physiological and therapeutic roles. J Clin Med. 2020;9(4):1014.Google Scholar
de Rooij, DG, Russell, LD. All you wanted to know about spermatogonia but were afraid to ask. J Androl. 2000;21(6):776–798.CrossRefGoogle ScholarPubMed
Boitani, C, Di, PS, Esposito, V, Vicini, E. Spermatogonial cells: mouse, monkey and man comparison. Semin Cell Dev Biol. 2016;59:79–88.Google Scholar
Clermont, Y. The cycle of the seminiferous epithelium in man. Am J Anat. 1963;112:35–51.CrossRefGoogle ScholarPubMed
Rowley, MJ, Heller, CG. Quantitation of the cells of the seminiferous epithelium of the human testis employing the sertoli cell as a constant. Z Zellforsch Mikrosk Anat. 1971;115(4):461–472.Google Scholar
Clermont, Y. Renewal of spermatogonia in man. Am J Anat. 1966;118(2):509–524.CrossRefGoogle ScholarPubMed
Hermann, BP, Sukhwani, M, Hansel, MC, Orwig, KE. Spermatogonial stem cells in higher primates: are there differences from those in rodents? Reproduction. 2010;139(3):479–493.Google Scholar
Clermont, Y. Two classes of spermatogonial stem cells in the monkey (Cercopithecus aethiops). Am J Anat. 1969;126(1):57–71.Google Scholar
van Alphen, MM, de Rooij, DG. Depletion of the seminiferous epithelium of the rhesus monkey, Macaca mulatta, after X-irradiation. Br J Cancer Suppl. 1986;7:102–104.Google Scholar
Di Persio, S, Saracino, R, Fera, S, et al. Spermatogonial kinetics in humans. Development. 2017;144(19):3430–3439.Google Scholar
Sohni, A, Tan, K, Song, HW, et al. The neonatal and adult human testis defined at the single-cell level. Cell Rep. 2019;26(6):1501–1517.Google Scholar
Muciaccia, B, Boitani, C, Berloco, BP, et al. Novel stage classification of human spermatogenesis based on acrosome development. Biol Reprod. 2013;89(3):60.CrossRefGoogle ScholarPubMed
Nihi, F, Gomes, MLM, Carvalho, FAR, et al. Revisiting the human seminiferous epithelium cycle. Hum Reprod. 2017;32(6):1170–1182.Google Scholar
Clermont, Y, Bustos-Obregon, E. Re-examination of spermatogonial renewal in the rat by means of seminiferous tubules mounted “in toto.” Am J Anat. 1968;122(2):237–247.Google Scholar
Bolcun-Filas, E, Handel, MA. Meiosis: the chromosomal foundation of reproduction. Biol Reprod. 2018;99(1):112–126.Google Scholar
Barchi, M, Mahadevaiah, S, Di, GM, et al. Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage. Mol Cell Biol. 2005;25(16):7203–7215.CrossRefGoogle ScholarPubMed
Tsai, MC, Cheng, YS, Lin, TY, Yang, WH, Lin, YM. Clinical characteristics and reproductive outcomes in infertile men with testicular early and late maturation arrest. Urology. 2012;80(4):826–832.CrossRefGoogle ScholarPubMed
Gershoni, M, Hauser, R, Barda, S, et al. A new MEIOB mutation is a recurrent cause for azoospermia and testicular meiotic arrest. Hum Reprod. 2019;34(4):666–671.CrossRefGoogle ScholarPubMed
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(2):342–351.CrossRefGoogle ScholarPubMed
Riera-Escamilla, A, Enguita-Marruedo, A, Moreno-Mendoza, D, et al. Sequencing of a ‘mouse azoospermia’ gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest. Hum Reprod. 2019;34(6):978–988.Google Scholar
Jan, SZ, Jongejan, A, Korver, CM, et al. Distinct prophase arrest mechanisms in human male meiosis. Development. 2018;145(16).Google ScholarPubMed
Sarrate, Z, Sole, M, Vidal, F, Anton, E, Blanco, J. Chromosome positioning and male infertility: it comes with the territory. J Assist Reprod Genet. 2018;35(11):1929–1938.CrossRefGoogle ScholarPubMed
Wang, Y, Wang, H, Zhang, Y, et al. Reprogramming of meiotic chromatin architecture during spermatogenesis. Mol Cell. 2019;73(3):547–561.Google Scholar
Vara, C, Paytuvi-Gallart, A, Cuartero, Y, et al. Three-dimensional genomic structure and cohesin occupancy correlate with transcriptional activity during spermatogenesis. Cell Rep. 2019;28(2):352–367.Google Scholar
Clermont, Y, Leblond, CP. Spermiogenesis of man, monkey, ram and other mammals as shown by the periodic acid-Schiff technique. Am J Anat. 1955;96(2):229–253.Google Scholar
Lehti, MS, Sironen, A. Formation and function of the manchette and flagellum during spermatogenesis. Reproduction. 2016;151(4):R43–R54.Google Scholar
Pleuger, C, Lehti, MS, Dunleavy, JE, Fietz, D, O’Bryan, MK. Haploid male germ cells-the Grand Central Station of protein transport. Hum Reprod Update. 2020;26(4):474–500.Google Scholar
Bao, J, Bedford, MT. Epigenetic regulation of the histone-to-protamine transition during spermiogenesis. Reproduction. 2016;151(5):R55–R70.Google Scholar
Monesi, V. Ribonucleic acid synthesis during mitosis and meiosis in the mouse testis. J Cell Biol. 1964;22:521–532.Google Scholar
Oliva, R. Protamines and male infertility. Hum Reprod Update. 2006;12(4):417–435.Google Scholar
Carrell, DT, Emery, BR, Hammoud, S. Altered protamine expression and diminished spermatogenesis: what is the link? Hum Reprod Update. 2007;13(3):313–327.Google Scholar
Heller, CG, Clermont, Y. Spermatogenesis in man: an estimate of its duration. Science. 1963;140(3563):184–186.Google Scholar
Russell, LD, Ettlin, RA, Hikim, APS, Clegg, ED. Histological and histopathological evaluation of the testis. J Androl. 1993;17(6):615–627.Google Scholar
Heller, CH, Clermont, Y. Kinetics of the germinal epithelium in man. Recent Prog Horm Res. 1964;20:545–575.Google Scholar
Suzuki, S, Diaz, VD, Hermann, BP. What has single-cell RNA-seq taught us about mammalian spermatogenesis? Biol Reprod. 2019;101(3):617–634.Google Scholar
Jan, SZ, Vormer, TL, Jongejan, A, et al. Unraveling transcriptome dynamics in human spermatogenesis. Development. 2017;144(20):3659–3673.Google Scholar
Shami, AN, Zheng, X, Munyoki, SK, et al. Single-cell RNA sequencing of human, macaque, and mouse testes uncovers conserved and divergent features of mammalian spermatogenesis. Dev Cell. 2020;54(4):529–547.Google Scholar
Amann, RP. The cycle of the seminiferous epithelium in humans: a need to revisit? J Androl. 2008;29(5):469–487.Google Scholar
Guo, J, Grow, EJ, Mlcochova, H, et al. The adult human testis transcriptional cell atlas. Cell Res. 2018;28(12):1141–1157.Google Scholar
Hermann, BP, Cheng, K, Singh, A, et al. The mammalian spermatogenesis single-cell transcriptome, from spermatogonial stem cells to spermatids. Cell Rep. 2018;25(6):1650–1667.Google Scholar
Goldmann, JM, Veltman, JA, Gilissen, C. De novo mutations reflect development and aging of the human germline. Trends Genet. 2019;35(11):828–839.Google Scholar
Xia, B, Yan, Y, Baron, M, et al. Widespread transcriptional scanning in the testis modulates gene evolution rates. Cell. 2020;180(2):248–262.CrossRefGoogle ScholarPubMed
Svejstrup, JQ. Mechanisms of transcription-coupled DNA repair. Nat Rev Mol Cell Biol. 2002;3(1):21–29.Google Scholar
Gille, AS, Lapoujade, C, Wolf, JP, Fouchet, P, Barraud-Lange, V. Contribution of single-cell transcriptomics to the characterization of human spermatogonial stem cells: toward an application in male fertility regenerative medicine? Int J Mol Sci. 2019;20(22):5773.Google Scholar
Soraggi, S, Riera, M, Rajpert-De, ME, Schierup, MH, Almstrup, K. Evaluating genetic causes of azoospermia: what can we learn from a complex cellular structure and single-cell transcriptomics of the human testis? Hum Genet. 2021;140(1):183–201.Google Scholar

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