Abstract
Highly differentiated spermatozoa are generated through multiple cellular and molecular processes maintained by Sertoli cells. The cellular events associated with germ cells include proliferation, protein folding and transportation, as well as sequential changes in chromatin and cell organelles. These processes are strictly controlled by the expression of specific genes, including transcription and DNA replication/repair. This complex spermatogenesis is impaired by a mutation such as gene knockout, which leads to a variety of morphological and functional abnormalities found in mature spermatozoa. An overview of spermatogenesis impairment induced by gene knockout is provided in the present review.
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References
Adham IM, Nayernia K, Burkhardt-Goetges E et al. (2001) Teratozoospermia in mice lacking the transition protein 2 (Tnp2). Mol Hum Reprod 7, 513–20.
Andersen OM, Yeung C-H, Vorum H et al. (2003) Essential role of the apolipoprotein E receptor-2 in sperm development. J Biol Chem 278, 23 989–95.
Behrens A, Genoud N, Naumann H et al. (2002) Absence of the prion protein homologue Doppel causes male sterility. EMBO J 21, 3652–8.
Celeste A, Petersen S, Romanienko PJ et al. (2002) Genomic instability in mice lacking histone H2AX. Science 296, 922–7.
Cho C, Bunch Do, Faure JE et al. (1998) Fertilization defects in sperm from mice lacking fertilin beta. Science 281, 1857–9.
Cooke HJ, Saunders PT (2002) Mouse models of male infertility. Nat Rev Genet 3, 790–801.
De Kretser DM, Baker HW (1999) Infertility in men: Recent advances and continuing controversies. J Clin Endocrinol Metab 84, 3443–50.
Deng W, Lin H (2002) miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell 2, 819–30.
Dix DJ, Allen JW, Collins BW et al. (1997) HSP70-2 is required for desynapsis of synaptonemal complexes during meiotic prophase in juvenile and adult mouse spermatocytes. Development 124, 4595–603.
Edelmann W, Cohen PE, Kane M et al. (1996) Meiotic pachytene arrest in MLH1-deficient mice. Cell 85, 1125–34.
Escalier D (2001) Impact of genetic engineering on the understanding of spermatogenesis. Hum Reprod Update 7, 191–210.
Fukami K, Nakao K, Inoue T et al. (2001) Requirement of phospholipase C delta 4 for the zona pellucida-induced acrosome reaction. Science 292, 920–3.
Guardavaccaro D, Kudo Y, Boulaire J et al. (2003) Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Dev Cell 4, 799–812.
Hagaman JP, Moyer JS, Bachman ES et al. (1998) Angiotensinconverting enzyme and male fertility. Proc Natl Acad Sci USA 95, 2552–7.
Hellsten E, Evans JP, Bernard DJ, Janne PA, Nussbaum RL (2001) Disrupted sperm function and fertilin beta processing in mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b. Dev Biol 240, 641–53.
Igakura T, Kadomatsu K, Kaname T et al. (1998) A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis. Dev Biol 194, 152–65.
Ikawa M, Nakanishi T, Yamada S et al. (1997) Calmegin is required for fertilin / heterodimerization and sperm fertility. Dev Biol 240, 254–61.
Juneja SC, Barr KJ, Enders GC, Kidder GM (1999) Defects in the germ line and gonads of mice lacking connexin43. Biol Reprod 60, 1263–70.
Kallio M, Chang Y, Manuel M et al. (2002) Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice. EMBO J 21, 2591–601.
Kang-Decker N, Mantchev GT, Juneja SC, McNiven MA, van Deursen JMA (2001) Lack of acrosome formation in Hrbdeficient mice. Science 294, 1531–3.
Kimura T, Ito C, Watanabe S et al. (2003) Mouse germ cell-less as an essential component for nuclear integrity. Mol Cell Biol 23, 1304–15.
Kobayashi Y, Watanabe M, Okada Y et al. (2002) Hydrocephalus, situs inversus, chronic sinusitis, and male infertility in DNA polymerase lambda-deficient mice: Possible implication for the pathogenesis of immotile cilia syndrome. Mol Cell Biol 22, 2769–76.
Kroft TL, Patterson J, Won Yoon J et al. (2001) GLI1 localization in the germinal epithelial cells alternates between cytoplasm and nucleus: Upregulation in transgenic mice blocks spermatogenesis in pachytene. Biol Reprod 65, 1663–71.
Lu Q, Shur BD (1997) Sperm from ?1,4-galactosyltransferasenull are refractory to ZP3-induced acrosome reactions and penetrate the zona pellucida poorly. Development 124, 4121–31.
Maekawa M, Suzuki-Toyota F, Toyama Y et al. (1998) Stagespecific localization of basigin, a member of the immunoglobulin superfamily, during mouse spermatogenesis. Arch Histol Cytol 61, 405–15.
Martianov I, Brancorsini S, Gansmuller A, Parvinen M, Davidson I, Sassone-Corsi P (2002) Distinct functions of TBP and TLF/ TRF2 during spermatogenesis: Requirement of TLF for heterochromatic chromocenter formation in haploid round spermatids. Development 129, 945–55.
McBurney MW, Yang X, Jardine K, Bieman M, Th’ng J, Lemieux M (2003) The absence of SIR2 protein has no effect on global gene silencing in mouse embryonic stem cells. Mol Cancer Res 1, 402–9.
Miki K, Willis WD, Brown PR, Goulding EH, Fulcher KD, Eddy EM (2002) Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility. Dev Biol 248, 331–42.
Nakamura T, Yao R, Ogawa T et al. (2004) Oligo-asthenoteratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta. Nat Genet 36, 528–33.
Nantel F, Sassone-Corsi P (1996) CREM: A transcriptional master switch during the spermatogenesis differentiation program. Front Biosci 1, 266–9.
Nayernia K, Adham IM, Burkhardt-Goettges E et al. (2002) Asthenozoospermia in mice with targeted deletion of the sperm mitochondrion-associated cysteine-rich protein (Smcp) gene. Mol Cell Biol 22, 3046–52.
Neesen J, Kirschner R, Ochs M et al. (2001) Disruption of an inner arm dynein heavy chain gene results in asthenozoospermia and reduced ciliary beat frequency. Hum Mol Genet 10, 1117–28.
Ng JM, Vrieling H, Sugasawa K et al. (2002) Developmental defects and male sterility in mice lacking the ubiquitin-like DNA repair gene mHR23B. Mol Cell Biol 22, 1233–45.
Nishimura H, Cho C, Branciforte DR, Myles DG, Primakoff P (2001) Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin beta. Dev Biol 233, 204–13.
Ren D, Navarro B, Perez G et al. (2001) A sperm ion channel required for sperm motility and male fertility. Nature 413, 603–9.
Roest HP, van Klaveren J, de Wit J et al. (1996) Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification. Cell 86, 799–810.
Romanienko PJ, Camerini-Otero RD (2000) The mouse Spo11 gene is required for meiotic chromosome synapsis. Mol Cell 6, 975–87.
Sapiro R, Kostetskii I, Olds-Clarke P, Gerton GL, Radice GL, Strauss JF (2002) Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6. Mol Cell Biol 22, 6298–305.
Sassone-Corsi P (2000) CREM: A master-switch regulating the balance between differentiation and apoptosis in male germ cells. Mol Reprod Dev 56, 228–9.
Saxena DK, Oh-Oka T, Kadomatsu K, Muramatsu T, Toshimori K (2002) Behaviour of a sperm surface transmembrane glycoprotein basigin during epididymal maturation and its role in fertilization in mice. Reproduction 123, 435–44.
Tajima Y, Onoue H, Kitamura Y, Nishimune Y (1991) Biologically active kit ligand growth factor is produced by mouse Sertoli cells and is defective in Sld mutant mice. Development 113, 1031–5.
Toyama Y, Maekawa M, Kadomatsu K, Miyauchi T, Muramatsu T, Yuasa S (1999) Histological characterization of defective spermatogenesis in mice lacking the basigin gene. Anat Histol Embryol 28, 205–13.
Tsuda M, Sasaoka Y, Kiso M et al. (2003) Conserved role of nanos proteins in germ cell development. Science 301, 1239–41.
Uhrin P, Dewerchin M, Hilpert M et al. (2000) Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility. J Clin Invest 106, 1531–9.
Venables JP, Cooke HJ (2000) Lessons from knockout and transgenic mice for infertility in men. J Endocrinol Invest 23, 584–91.
Vogel T, Speed RM, Ross A, Cooke HJ (2002) Partial rescue of the Dazl knockout mouse by the human DAZL gene. Mol Hum Reprod 8, 797–804.
Vollrath B, Pudney J, Asa S, Leder P, Fitzgerald K (2001) Isolation of a murine homologue of the Drosophila neuralized gene, a gene required for axonemal integrity in spermatozoa and terminal maturation of the mammary gland. Mol Cell Biol 21, 7481–94.
Watson ML, Zinn AR, Inoue N et al. (1998) Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse. Proc Natl Acad Sci USA 95, 14 361–6.
World Health Organization (1999) WHO Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction, 4th edn. Cambridge University Press, New York.
Wu JY, Ribar TJ, Cummings DE, Burton KA, McKnight GS, Means AR (2000) Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking Camk4. Nat Genet 25, 448–52.
Xu X, Toselli PA, Russell LD, Seldin DC (1999) Globozoospermia in mice lacking the casein kinase II alph’a?catalytic subunit. Nat Genet 23, 118–21.
Yan W, Assadi AH, Wynshaw-Boris A, Eichele G, Matzuk MM, Clark GD (2003) Previously uncharacterized roles of plateletactivating factor acetylhydrolase 1b complex in mouse spermatogenesis. Proc Natl Acad Sci USA 100, 7189–94.
Yao R, Ito C, Natsume Y et al. (2002) Lack of acrosome formation in mice lacking a Golgi protein, GOPC. Proc Natl Acad Sci USA 99, 11 211–16.
Yu YE, Zhang Y, Unni E et al. (2000) Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice. Proc Natl Acad Sci USA 97, 4683–8.
Yuan L, Liu JG, Zhao J, Brundell E, Daneholt B, Hoog C (2000) The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 5, 73–83.
Zhang D, Penttila TL, Morris PL, Teichmann M, Roeder RG (2001) Spermiogenesis deficiency in mice lacking the Trf2 gene. Science 292, 1153–5.
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Toshimori, K., Ito, C., Maekawa, M. et al. Impairment of spermatogenesis leading to infertility. Anato Sci Int 79, 101–111 (2004). https://doi.org/10.1111/j.1447-073x.2004.00076.x
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DOI: https://doi.org/10.1111/j.1447-073x.2004.00076.x