5 - Spermatogenesis in the adult  pp. 74-89

Spermatogenesis in the adult

By Joseph P. Alukal, Dolores J. Lamb, Craig S. Niederberger and Antoine A. Makhlouf

Chapter Abstract

In mammals, spermatogenesis begins with diploid stem cells that resemble other somatic cells; it ends with highly specialized motile haploid cells that are remarkably unique in appearance and function. Continuous production of spermatozoa throughout life requires that spermatogonia replenish themselves. Type B spermatogonia undergo mitosis to give rise to diploid primary spermatocytes. The spermatocytes then cross the blood-testis barrier formed by the Sertoli tight junctions to the adluminal compartment. Spermiogenesis refers to the acquisition by the germ cell of several organelles and accessory structures such as the acrosome and the flagellum. Testosterone and follicle-stimulating hormone (FSH) are the two major regulatory hormones of spermatogenesis. FSH binding to its receptor activates adenylate cyclase, and the resultant rise in cAMP triggers binding of cAMP response element modulator (CREM) to ACT (activator of CREM). The complex then acts as a molecular master-switch for a number of genes involved in spermatogenesis.


cAMP response element modulator; follicle-stimulating hormone; somatic cells; blood-testis barrier; mitosis; spermatogenesis; flagellum; acrosome; spermatocytes;
Abou-Haila A, Tulsiani DR. Mammalian sperm acrosome: formation, contents, and function. Arch Biochem Biophys 2000; 379: 173–82.
Akbarsha MA, Latha PN, Murugaian P. Retention of cytoplasmic droplet by rat cauda epididymal spermatozoa after treatment with cytotoxic and xenobiotic agents. J Reprod Fertil 2000; 120: 385–90.
Amann RP,Howards SS. Daily spermatozoal production and epididymal spermatozoal reserves of the human male. J Urol 1980; 124: 211–15.
Aoki VW, Emery BR, Liu L., Carrell DT. Protamine levels vary between individual sperm cells of infertile human males and correlate with viability and DNA integrity. J Androl 2006; 27: 890–8.
Aponte PM, van Bragt MP, de Rooij DG, van Pelt AM. Spermatogonial stem cells: characteristics and experimental possibilities. APMIS 2005; 113: 727–42.
Balhorn R., Reed S, Tanphaichitr N. Aberrant protamine 1/protamine 2 ratios in sperm of infertile human males. Experientia 1988; 44: 52–5.
Barlow AL, Hulten MA. Crossing over analysis at pachytene in man. Eur J Hum Genet 1998; 6: 350–8.
Baudat F., Manova K, Yuen JP, Jasin M., Keeney S. Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Mol Cell 2000; 6: 989–98.
Biggiogera M., Fakan S, Leser G., Martin TE, Gordon J. Immunoelectron microscopical visualization of ribonucleoproteins in the chromatoid body of mouse spermatids. Mol Reprod Dev 1990; 26: 150–8.
Blendy JA, Kaestner KH, Weinbauer GF, Nieschlag E., Schütz G. Severe impairment of spermatogenesis in mice lacking the CREM gene. Nature 1996; 380: 162–5.
Bowen RH. On the idiosome, Golgi apparatus and acrosome in the male germ cells. The Anatomical Record 1922; 24: 158–160.
Breucker H., Schafer E, Holstein AF. Morphogenesis and fate of the residual body in human spermiogenesis. Cell Tissue Res 1985; 240: 303–9.
Brinster RL, Avarbock MR. Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci U S A 1994; 91: 11303–7.
Brinster RL, Zimmermann JW. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci U S A 1994; 91: 11298–302.
Carrell DT, Liu L. Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl 2001; 22: 604–10.
Carrell DT, Liu L., Peterson CM, et al. Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss. Arch Androl 2003; 49: 49–55.
Chen C., Ouyang W, Grigura V., et al. ERM is required for transcriptional control of the spermatogonial stem cell niche. Nature 2005; 436: 1030–4.
Chiarini-Garcia H, Russell LD. High-resolution light microscopic characterization of mouse spermatogonia. Biol Reprod 2001; 65: 1170–8.
Cho C., Willis WD, Goulding EH, et al. Haploinsufficiency of protamine-1 or -2 causes infertility in mice. Nat Genet 2001; 28: 82–6.
Chung SS, Wang X., Wolgemuth DJ. Male sterility in mice lacking retinoic acid receptor alpha involves specific abnormalities in spermiogenesis. Differentiation 2005; 73: 188–98.
Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 1972; 52: 198–236.
Clermont Y. Renewal of spermatogonia in man. Am J Anat 1966; 118: 509–24.
Clermont Y. Spermatogenesis in man: a study of the spermatogonial population. Fertil Steril 1966; 17: 705–21.
Clermont Y. The cycle of the seminiferous epithelium in man. Am J Anat 1963; 112: 35–51.
Corzett M., Mazrimas J, Balhorn R. Protamine 1: protamine 2 stoichiometry in the sperm of eutherian mammals. Mol Reprod Dev 2002; 61: 519–27.
Coviello AD, Bremner WJ, Matsumoto AM, et al. Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen. J Androl 2004; 25: 931–8.
D'Occhio MJ, Hengstberger KJ, Johnston SD. Biology of sperm chromatin structure and relationship to male fertility and embryonic survival. Anim Reprod Sci 2007; 101: 1–17.
Dadoune JP. Expression of mammalian spermatozoal nucleoproteins. Microsc Res Tech 2003; 61: 56–75.
De Gendt K., Atanassova N, Tan KA, et al. Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective or total ablation of the androgen receptor. Endocrinology 2005; 146: 4117–26.
De Gendt K., Swinnen JV, Saunders PT, et al. A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci USA 2004; 101: 1327–32.
de Rooij DG, Russell LD. All you wanted to know about spermatogonia but were afraid to ask. J Androl 2000; 21: 776–98.
DeJong J. Basic mechanisms for the control of germ cell gene expression. Gene 2006; 366: 39–50.
Denolet E., De Gendt K., Allemeersch J, et al. The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice. Mol Endocrinol 2006; 20: 321–34.
Dierich A., Sairam MR, Monaco L., et al. Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc Natl Acad Sci USA 1998; 95: 13612–17.
Dobrinski I. Germ cell transplantation and testis tissue xenografting in domestic animals. Anim Reprod Sci 2005; 89: 137–45.
Eddy E. The spermatozoon. In: Neill JD, ed. Knobil and Neill's Physiology of Reproduction, 3rd edn. New York, NY: Academic Press, 1994: 3–54.
Eddy EM, Toshimori K., O'Brien DA. Fibrous sheath of mammalian spermatozoa. Microsc Res Tech 2003; 61: 103–15.
Eddy EM. Male germ cell gene expression. Recent Prog Horm Res 2002; 57: 103–28.
Ehmcke J., Simorangkir DR, Schlatt S. Identification of the starting point for spermatogenesis and characterization of the testicular stem cell in adult male rhesus monkeys. Hum Reprod 2005; 20: 1185–93.
Eijpe M., Offenberg H, Jessberger R., Revenkova E, Heyting C. Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3. J Cell Biol 2003; 160: 657–70.
Escalier D. New insights into the assembly of the periaxonemal structures in mammalian spermatozoa. Biol Reprod 2003; 69: 373–8.
Esposito MS, Esposito RE. The genetic control of sporulation in Saccharomyces. I. The isolation of temperature-sensitive sporulation-deficient mutants. Genetics 1969; 61: 79–89.
Fawcett DW. The mammalian spermatozoon. Dev Biol 1975; 44: 394–436.
Foulkes NS, Mellström B, Benusiglio E., Sassone-Corsi P. Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature 1992; 355: 80–4.
Gonsalves J., Sun F, Schlegel PN, et al. Defective recombination in infertile men. Hum Mol Genet 2004; 13: 2875–83.
Haering CH, Nasmyth K. Building and breaking bridges between sister chromatids. Bioessays 2003; 25: 1178–91.
Hammadeh ME, Zeginiadov T., Rosenbaum P, et al. Predictive value of sperm chromatin condensation (aniline blue staining) in the assessment of male fertility. Arch Androl 2001; 46: 99–104.
Hays FA, Watson J., Ho PS. Caution! DNA crossing: crystal structures of Holliday junctions. J Biol Chem 2003; 278: 49663–6.
Heller CGClermont Y. Spermatogenesis in man: an estimate of its duration. Science 1963; 140: 184–6.
Heller CH, Clermont Y. Kinetics of the germinal epithelium in man. Recent Prog Horm Res 1964; 20: 545–75.
Hendriksen PJ, Hoogerbrugge JW, Baarends WM, et al. Testis-specific expression of a functional retroposon encoding glucose-6-phosphate dehydrogenase in the mouse. Genomics 1997; 41: 350–9.
Hermo L., Rambourg A, Clermont Y. Three-dimensional architecture of the cortical region of the Golgi apparatus in rat spermatids. Am J Anat 1980; 157: 357–73.
Hess RA, Cooke PS, Hofmann MC, Murphy KM. Mechanistic insights into the regulation of the spermatogonial stem cell niche. Cell Cycle 2006; 5: 1164–70.
Hew KW, Ericson WA, Welsh MJ. A single low cadmium dose causes failure of spermiation in the rat. Toxicol Appl Pharmacol 1993; 121: 15–21.
Holstein AF, Schulze W., Davidoff M. Understanding spermatogenesis is a prerequisite for treatment. Reprod Biol Endocrinol 2003; 1: 107.
Hu J., Shima H, Nakagawa H. Glial cell line-derived neurotropic factor stimulates sertoli cell proliferation in the early postnatal period of rat testis development. Endocrinology 1999; 140: 3416–21.
Huckins C. The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. Anat Rec 1971; 169: 533–57.
Hummelke GC, Cooney AJ. Germ cell nuclear factor is a transcriptional repressor essential for embryonic development. Front Biosci 2001; 6: D1186–91.
Hummelke GC, Cooney AJ. Reciprocal regulation of the mouse protamine genes by the orphan nuclear receptor germ cell nuclear factor and CREMtau. Mol Reprod Dev 2004; 68: 394–407.
Hummelke GC, Meistrich ML, Cooney AJ. Mouse protamine genes are candidate targets for the novel orphan nuclear receptor, germ cell nuclear factor. Mol Reprod Dev 1998; 50: 396–405.
Irons MJ, Clermont Y. Formation of the outer dense fibers during spermiogenesis in the rat. Anat Rec 1982; 202: 463–71.
Jarow JP, Zirkin BR. The androgen microenvironment of the human testis and hormonal control of spermatogenesis. Ann N Y Acad Sci 2005; 1061: 208–20.
Keeney S., Giroux CN, Kleckner N. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 1997; 88: 375–84.
Kerr JB, et al. Cytology of the testis and intrinsic control mechanisms. In: Neill JD, ed. Knobil and Neill's Physiology of Reproduction, 3rd edn. New York, NY: Academic Press, 1994: 827–947.
Khaira H., McLean D, Ohl DA, Smith GD. Spermatogonial stem cell isolation, storage, and transplantation. J Androl 2005; 26: 442–50.
Kimura Y., Yanagimachi R. Development of normal mice from oocytes injected with secondary spermatocyte nuclei. Biol Reprod 1995; 53: 855–62.
Kleckner N., Storlazzi A, Zickler D. Coordinate variation in meiotic pachytene SC length and total crossover/chiasma frequency under conditions of constant DNA length. Trends Genet 2003; 19: 623–8.
Klemm U., Muller-Esterl W, Engel W. Acrosin, the peculiar sperm-specific serine protease. Hum Genet 1991; 87: 635–41.
Kodama H., Yamaguchi R, Fukuda J., Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil Steril 1997; 68: 519–24.
Kotaja N., Bhattacharyya SN, Jaskiewicz L., et al. The chromatoid body of male germ cells: similarity with processing bodies and presence of Dicer and microRNA pathway components. Proc Natl Acad Sci USA 2006; 103: 2647–52.
Kotaja N., Sassone-Corsi P. The chromatoid body: a germ-cell-specific RNA-processing centre. Nat Rev Mol Cell Biol 2007; 8: 85–90.
Kumar TR, Low MJ, Matzuk MM. Genetic rescue of follicle-stimulating hormone beta-deficient mice. Endocrinology 1998; 139: 3289–95.
Kumar TR, Wang Y., Lu N, Matzuk MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 1997; 15: 201–4.
Leblond CP, Clermont Y. Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann N Y Acad Sci 1952; 55: 548–73.
Lei ZM, Mishra S., Zou W, et al. Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene. Mol Endocrinol 2001; 15: 184–200.
Lennox B., Ahmad KN. The total length of tubules in the human testis. J Anat 1970; 107: 191.
Lo KC, Brugh VM, Parker M., Lamb DJ. Isolation and enrichment of murine spermatogonial stem cells using rhodamine 123 mitochondrial dye. Biol Reprod 2005; 72: 767–71.
Lynn A., Koehler KE, Judis L., et al. Covariation of synaptonemal complex length and mammalian meiotic exchange rates. Science 2002; 296: 2222–5.
Ma X., Dong Y, Matzuk MM, Kumar TR. Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility. Proc Natl Acad Sci USA 2004; 101: 17294–9.
Martianov I., Fimia GM, Dierich A., et al. Late arrest of spermiogenesis and germ cell apoptosis in mice lacking the TBP-like TLF/TRF2 gene. Mol Cell 2001; 7: 509–15.
McCarrey JR, Thomas K. Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature 1987; 326: 501–5.
McLachlan RI, O'Donnell L, Meachem SJ, et al. Identification of specific sites of hormonal regulation in spermatogenesis in rats, monkeys, and man. Recent Prog Horm Res 2002; 57: 149–79.
Meistrich ML, Mohapatra B., Shirley CR, Zhao M. Roles of transition nuclear proteins in spermiogenesis. Chromosoma 2003; 111: 483–8.
Meng X., Lindahl M, Hyvönen ME, et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science, 2000. 287: 1489–93.
Michaelis C., Ciosk R, Nasmyth K. Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 1997; 91: 35–45.
Monaco L., Kotaja N, Fienga G., et al. Specialized rules of gene transcription in male germ cells: the CREM paradigm. Int J Androl 2004; 27: 322–7.
Morales CR, Oko R., Clermont Y. Molecular cloning and developmental expression of an mRNA encoding the 27 kDa outer dense fiber protein of rat spermatozoa. Mol Reprod Dev 1994; 37: 229–40.
Moreno RD, Alvarado CP. The mammalian acrosome as a secretory lysosome: new and old evidence. Mol Reprod Dev 2006; 73: 1430–4.
Muller J., Skakkebaek NE. Quantification of germ cells and seminiferous tubules by stereological examination of testicles from 50 boys who suffered from sudden death. Int J Androl 1983; 6: 143–56.
Nagano M., Brinster CJ, Orwig KE, et al. Transgenic mice produced by retroviral transduction of male germ-line stem cells. Proc Natl Acad Sci U S A 2001; 98: 13090–5.
Nagano M., McCarrey JR, Brinster RL. Primate spermatogonial stem cells colonize mouse testes. Biol Reprod 2001; 64: 1409–16.
Naughton CK, Jain S., Strickland AM, Gupta A., Milbrandt J. Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate. Biol Reprod 2006; 74: 314–21.
Nistal M., Codesal J, Paniagua R., Santamaria L. Decrease in the number of human Ap and Ad spermatogonia and in the Ap/ Ad ratio with advancing age: new data on the spermatogonial stem cell. J Androl 1987; 8: 64–8.
O'Donnell L, et al. Endocrine regulation of spermatogenesis. In: Neill JD, ed. Knobil and Neill's Physiology of Reproduction, 3rd edn. New York, NY: Academic Press, 1994: 1017–69.
Ohta H., Yomogida K, Dohmae K., Nishimune Y. Regulation of proliferation and differentiation in spermatogonial stem cells: The role of c-kit and its ligand SCF. Development 2000; 127: 2125–31.
Oliva R. Protamines and male infertility. Hum Reprod Update 2006; 12: 417–35.
Paniagua R., Nistal M. Morphological and histometric study of human spermatogonia from birth to the onset of puberty. J Anat 1984; 139: 535–52.
Parvinen M. The chromatoid body in spermatogenesis. Int J Androl 2005; 28: 189–201.
Parvinen M., Parvinen LM. Active movements of the chromatoid body: a possible transport mechanism for haploid gene products. J Cell Biol 1979; 80: 621–8.
Pittman DL, Cobb J., Schimenti KJ, et al. Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog. Mol Cell 1998; 1: 697–705.
Prader A. Testicular size: assessment and clinical importance. Triangle 1966; 7: 240–3.
Print CG, Loveland KL. Germ cell suicide: new insights into apoptosis during spermatogenesis. Bioessays 2000; 22: 423–30.
Rey RA, Campo SM, Bedecarrás P, Nagle CA, Chemes HE. Is infancy a quiescent period of testicular development? Histological, morphometric, and functional study of the seminiferous tubules of the cebus monkey from birth to the end of puberty. J Clin Endocrinol Metab 1993; 76: 1325–31.
Richler C., Ast G, Goitein R., et al. Splicing components are excluded from the transcriptionally inactive XY body in male meiotic nuclei. Mol Biol Cell 1994; 5: 1341–52.
Russell L. Desmosome-like junctions between Sertoli and germ cells in the rat testis. Am J Anat 1977; 148: 301–12.
Russell LD. Further observations on tubulobulbar complexes formed by late spermatids and Sertoli cells in the rat testis. Anat Rec 1979; 194: 213–32.
Saito K., O'Donnell L, McLachlan RI, Robertson DM. Spermiation failure is a major contributor to early spermatogenic suppression caused by hormone withdrawal in adult rats. Endocrinology 2000; 141: 2779–85.
Sakai Y., Yamashina S. Mechanism for the removal of residual cytoplasm from spermatids during mouse spermiogenesis. Anat Rec 1989; 223: 43–8.
Sakkas D., Urner F, Bianchi PG, et al. Sperm chromatin anomalies can influence decondensation after intracytoplasmic sperm injection. Hum Reprod 1996; 11: 837–43.
Schrans-Stassen BH, van de Kant HJ, de Rooij DG, van Pelt AM. Differential expression of c-kit in mouse undifferentiated and differentiating type A spermatogonia. Endocrinology 1999; 140: 5894–900.
Schulze C. Morphological characteristics of the spermatogonial stem cells in man. Cell Tissue Res 1979; 198: 191–9.
Schulze W. Evidence of a wave of spermatogenesis in human testis. Andrologia 1982; 14: 200–7.
Shao X., Tarnasky HA, Lee JP, Oko R., van der Hoorn FA. Spag4, a novel sperm protein, binds outer dense-fiber protein Odf1 and localizes to microtubules of manchette and axoneme. Dev Biol 1999; 211: 109–23.
Shao X., van der Hoorn FA. Self-interaction of the major 27-kilodalton outer dense fiber protein is in part mediated by a leucine zipper domain in the rat. Biol Reprod 1996; 55: 1343–50.
Shimizu Y., Motohashi N, Iseki H., et al. A novel subpopulation lacking Oct. 4 expression in the testicular side population. Int J Mol Med 2006; 17: 21–8.
Shinohara T., Orwig KE, Avarbock MR, Brinster RL. Spermatogonial stem cell enrichment by multiparameter selection of mouse testis cells. Proc Natl Acad Sci U S A 2000; 97: 8346–51.
Sofikitis N., Mantzavinos T, Loutradis D., et al. Ooplasmic injections of secondary spermatocytes for non-obstructive azoospermia. Lancet 1998; 351: 1177–8.
Solari AJ. The behavior of the XY pair in mammals. Int Rev Cytol 1974; 38: 273–317.
Steinberger E., Root A, Ficher M., Smith KD. The role of androgens in the initiation of spermatogenesis in man. J Clin Endocrinol Metab 1973; 37: 746–51.
Sugiura S., Kashiwabara S, Iwase S., Baba T. Expression of a testis-specific form of TBP-related factor 2 (TRF2) mRNA during mouse spermatogenesis. J Reprod Dev 2003; 49: 107–11.
Sun JG, Jurisicova A., Casper RF. Detection of deoxyribonucleic acid fragmentation in human sperm: Correlation with fertilization in vitro. Biol Reprod 1997; 56: 602–7.
Sutovsky P. Ubiquitin-dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: Killing three birds with one stone. Microsc Res Tech 2003; 61: 88–102.
Sutovsky P.,Manandhar G. Mammalian spermatogenesis and sperm structure: anatomical and compartmental analysis. In: Jonge CJD, Barratt CLR, eds. The Sperm Cell: Production, Maturation, Fertilization, Regeneration. Cambridge: Cambridge University Press, 2006: 1–30.
Tegelenbosch RA, de Rooij DG. A quantitative study of spermatogonial multiplication and stem cell renewal in the C3H/101 F1 hybrid mouse. Mutat Res 1993; 290: 193–200.
Tesarik J., Balaban B, Isiklar A., et al. In-vitro spermatogenesis resumption in men with maturation arrest: Relationship with in-vivo blocking stage and serum FSH. Hum Reprod 2000; 15: 1350–4.
Toshimori K. Biology of spermatozoa maturation: an overview with an introduction to this issue. Microsc Res Tech 2003; 61: 1–6.
Toshimori K., Ito C. Formation and organization of the mammalian sperm head. Arch Histol Cytol 2003; 66: 383–96.
Tulsiani DR, NagDas SK, Skudlarek MD, Orgebin-Crist MC. Rat sperm plasma membrane mannosidase: localization and evidence for proteolytic processing during epididymal maturation. Dev Biol 1995; 167: 584–95.
van Alphen MM, van de Kant HJ, de Rooij DG. Repopulation of the seminiferous epithelium of the rhesus monkey after X irradiation. Radiat Res 1988; 113: 487–500.
Wang PJ. X chromosomes, retrogenes and their role in male reproduction. Trends Endocrinol Metab 2004; 15: 79–83.
Watt FM, Hogan BL. Out of Eden: stem cells and their niches. Science 2000; 287: 1427–30.
Weber JE, Russell LD. A study of intercellular bridges during spermatogenesis in the rat. Am J Anat 1987; 180: 1–24.
Wine RN, Chapin RE. Adhesion and signaling proteins spatiotemporally associated with spermiation in the rat. J Androl 1999; 20: 198–213.
Yuan L., Liu JG, Zhao J., Brundell E, Daneholt B., Höög C. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 2000; 5: 73–83.
Zamore PD, Haley B. Ribo-gnome: the big world of small RNAs. Science 2005; 309: 1519–24.
Zhengwei Y., Wreford NG, Royce P., de Kretser DM, McLachlan RI. Stereological evaluation of human spermatogenesis after suppression by testosterone treatment: Heterogeneous pattern of spermatogenic impairment. J Clin Endocrinol Metab 1998; 83: 1284–91.