摘要
哺乳动物中,精子发生是一个复杂而且受到严格调控的过程,减数分裂前期Ⅰ,同源染色体的配对联会以及重组的发生十分重要,它可以确保同源染色体相互分离并最终形成正常的配子,重组发生的位置和数目异常时往往会导致异常配子的产生。同时,越来越多的研究表明小RNAs在精子发生过程中发挥重要作用,为探讨哺乳动物中遗传重组发生的机制以及精子发生过程中小RNAs可能的调控机制分别做了以下三部分工作：
1.麂科动物(Muntiacus, Cervidaei)-直被广泛用来研究染色体及核型演化,然而,对于它们减数分裂过程中同源染色体的行为,尤其是减数分裂重组的频率和分布模式知之甚少。本部分研究中,以中国麂(Muntiacus reevesi)为研究对象,利用微铺展法将其精母细胞联会复合体铺展开,结合免疫荧光技术,用联会复合体侧轴蛋白SCP3,错配修复蛋白MLH1以及着丝粒蛋白CREST的抗体来显示联会复合体以及重组位点和着丝粒的位置。对于170个粗线期细胞进行重组和分布模式分析,结果显示39.4%的XY二价体上没有重组位点,然而常染色体中只有0.5%没有重组位点,平均每个粗线期细胞重组位点数为29.8,范围为24-34；重组位点MLH1在联会复合体上的分布和其他哺乳动物相比存在差异：当一条联会复合体上有一个重组位点时,在联会复合体上分布相对分散；当联会复合体上有两个重组位点时,在亚端粒部位有一个较大的峰,而且总体上雄性中国麂重组位点间的干扰强度要低,这些都和雄性小鼠和人类男性中MLH1分布模式存在明显不同,提示在雄性中国麂中,同源染色体重组的模式和其他的哺乳动物有些许不同,这也为我们更深刻的理解哺乳动物减数分裂同源染色体重组(重组频率和重组数目)发生的机制提供很好的提供有利线索。
2.长期以来,减数分裂重组频率与联会复合体长度之间的关系一直是人们研究的兴趣所在,但二者之间相互关系却未被详尽的阐述过。为了更深入的探讨这一问题,我们测量了10个正常男性889个粗线期精母细胞中的19558条联会复合体长度,同时以MLH1作为重组的标记物,统计了联会复合体上的重组频率。我们看到二者之间有一个非常复杂的关系。在这10个人中有8个二者之间呈现正相关关系,其中有3个为较弱的正相关,其他5个为中等程度的正相关,在另外2个研究对象中,我们首次发现单个细胞中联会复合体长度与重组频率无相关性。而且,在不同人之间,甚至在同一个人的不同细胞之间,大多数联会复合体长度相似的细胞,其重组位点数目也不相同,反之亦然。本研究为阐述联会复合体长度和重组频率之间的关系提供了直接的证据,为以后研究二者之间机制关系提供有力的数据支持。
3. miRNAs是一类内源性RNA分子,可以在转录和转录后水平调控基因的表达。一直以来人们都致力于在各个物种中发现新的miRNAs并试图了解他们的功能。然而利用第二代深测序技术对于人类睾丸组织中miRNAs的表达谱至今没有相关报道。本部分研究旨在利用Solexa测序技术构建正常人类男性中miRNAs和piRNAs的表达谱。我们共检测到770条已知的miRNAs和5个条新的miRNAs以及20121条piRNAs,同时也表明人类睾丸组织中有大量的小RNAs存在。我们选择了15条已知的和5条新的miRNAs利用qRT-PCR来验证测序的可靠性。我们分析了表达较丰富的以及新的miRNAs的靶基因,并用GO分析预测这些基因可能参与的生物学过程。结果提示这些miRNA参与了很多重要的生物学过程,其中包括精子发生过程中的减数分裂以及p53中相关的调节通路。
Spermotogenesis is a complex and regulated progress in mammals. During meiosis I, meiotic pairing and recombination play a crucial role in holding homologous chromosomes together and guaranteeing their accurate segregation into daughter cells. Abnormalities in the frequency and location of crossovers are associated with non-disjunction of homologous chromosomes and the production of aneuploid gametes. In the study, in order to investigate the mechanisms of meiotic recombination and the possible roles of RNAs in spermatogenesis, we done the work including three parts:
1. The muntjacs (Muntiacus, Cervidae) have been extensively studied in terms of chromosomal and karyotypic evolution. However, little is known about their meiotic chromosomes particularly the recombination patterns of homologous chromosomes. Spermatocyte preparations were obtained from Chinese muntjac (Muntiacus reevesi) by a drying down spreading technique and immunostained to show synaptonemal complexes (SCs), recombination foci and kinetochores with antibodies against the SC protein SCP3, mismatch repair protein MLH1and kintochores, respectively. The mean number of MLH1foci on autosome SCs per cell was29.8, ranging from25-34.39.4%of XY bivalents lacked MLH1foci compared to less than0.5%of autosomes. The average number of MLH1foci per pachytene cell in M. reevesi was29.8. The distribution of MLH1foci differed from other mammals. On SCs with one focus, the distribution was more even in M. reevesi than in other mammals; for SCs that have two or more MLH1foci, usually there was a larger peak in the sub-centromere region than other regions on SC in M. reevesi. Additionally, there was a lower level of interference between foci in M. reevesithan in mouse or human. These observations may suggest that the regulation of homologous recombination in M. reevesiis slightly different from other mammals and will improve our understanding of the regulation of meiotic recombination, with respect to recombination frequency and position.
2. Although the relationship between meiotic recombination frequency and synaptonemal complex (SC) length has been of interest for a long time, how recombination frequency is related to SC length has not been carefully explored. To address this question, we have measured the meiotic recombination frequency as represented by MLH1foci in889pachytene spermatocytes and measured the length of19,558autosomal SCs from10human males. A complex relationship between the number of MLH1foci and total autosomal SC length per cell was observed. A positive correlation with significant correlation coefficients between the two variables was found in eight of the ten donors examined, with three donors showing weak correlation, and five showing moderate correlation. Two donors who did not show any correlation between the two variables were identified for the first time. Moreover, most cells with similar total autosomal SC length showed very different number s of MLH1foci both between individuals and even within an individual, and vice versa. Our data provide the first evidence for a complex relation-ship between the recombination frequency and total length of autosomal SCs per cell in human males.
3. MicroRNAs (miRNAs) are a class of small endogenous RNAs that play a regulatory role in cells by negatively affecting gene expression at transcriptional and post-transcriptional levels. There have been extensive studies aiming to discover miRNAs and to analyze their functions in cells from a variety of species. However, there are no published studies of miRNA profiles in human testis using next generation sequencing (NGS) technology. In this study, we employed Solexa sequencing technology to profile miRNAs in normal human testis. We detected770known and5novel human miRNAs, and20121piRNAs, indicating that the human testis has a complex population of small RNAs. The expression of miRNAs detected by NGS was validated by qRT-PCR of15known and5novel miRNAs. We have predicted potential target genes of the abundant known miRNAs and novel miRNAs and subjected them to GO and pathway analysis, revealing the involvement of miRNAs in many important biological functions including meiosis and p53-related pathways that are implicated in the regulation of spermatogenesis.
引文
1. Borner GV, Kleckner N, Hunter N (2004) Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117:29-45.
2. Martin RH (2005) Mechanisms of nondisjunction in human spermatogenesis. Cytogenet Genome Res 111:245-249.
3. Sloter E, Nath J, Eskenazi B, Wyrobek AJ (2004) Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents. Fertil Steril 81: 925-943.
4. Shi Q, Martin RH (2001) Aneuploidy in human spermatozoa:FISH analysis in men with constitutional chromosomal abnormalities, and in infertile men. Reproduction 121:655-666.
5. Lengronne A, Katou Y, Mori S, Yokobayashi S, Kelly GP, et al. (2004) Cohesin relocation from sites of chromosomal loading to places of convergent transcription. Nature 430:573-578.
6. Revenkova E, Eijpe M, Heyting C, Gross B, Jessberger R (2001) Novel meiosis-specific isoform of mammalian SMC1. Mol Cell Biol 21:6984-6998.
7. Sjogren C, Nasmyth K (2001) Sister chromatid cohesion is required for postreplicative double-strand break repair in Saccharomyces cerevisiae. Curr Biol 11:991-995.
8. Nasmyth K (2005) How do so few control so many? Cell 120:739-746.
9. Kitajima TS, Kawashima SA, Watanabe Y (2004) The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis. Nature 427:510-517.
10. Nasmyth K (2005) How might cohesin hold sister chromatids together? Philos Trans R Soc Lond B Biol Sci 360:483-496.
11. Waizenegger IC, Hauf S, Meinke A, Peters JM (2000) Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. Cell 103:399-410.
12. Uhlmann F, Lottspeich F, Nasmyth K (1999) Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1. Nature 400:37-42.
13. Watanabe Y, Kitajima TS (2005) Shugoshin protects cohesin complexes at centromeres. Philos Trans R Soc Lond B Biol Sci 360:515-521, discussion 521.
14. Rabitsch KP, Gregan J, Schleiffer A, Javerzat JP, Eisenhaber F, et al. (2004) Two fission yeast homologs of Drosophila Mei-S332 are required for chromosome segregation during meiosis I and II. Curr Biol 14:287-301.
15. Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, et al. (2006) Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441:46-52.
16. Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, et al. (2006) PP2A is required for centromeric localization of Sgol and proper chromosome segregation. Dev Cell 10:575-585.
17. Meuwissen RL, Offenberg HH, Dietrich AJ, Riesewijk A, van Iersel M, et al. (1992) A coiled-coil related protein specific for synapsed regions of meiotic prophase chromosomes. EMBO J 11:5091-5100.
18. Lammers JH, Offenberg HH, van Aalderen M, Vink AC, Dietrich AJ, et al. (1994) The gene encoding a major component of the lateral elements of synaptonemal complexes of the rat is related to X-linked lymphocyte-regulated genes. Mol Cell Biol 14:1137-1146.
19. Offenberg HH, Schalk JA, Meuwissen RL, van Aalderen M, Kester HA, et al. (1998) SCP2:a major protein component of the axial elements of synaptonemal complexes of the rat. Nucleic Acids Res 26:2572-2579.
20. Hamer G, Gell K, Kouznetsova A, Novak I, Benavente R, et al. (2006) Characterization of a novel meiosis-specific protein within the central element of the synaptonemal complex. J Cell Sci 119:4025-4032.
21. Wang PJ, McCarrey JR, Yang F, Page DC (2001) An abundance of X-linked genes expressed in spermatogonia. Nat Genet 27:422-426.
22. Bolcun-Filas E, Costa Y, Speed R, Taggart M, Benavente R, et al. (2007) SYCE2 is required for synaptonemal complex assembly, double strand break repair, and homologous recombination. J Cell Biol 176:741-747.
23. Yuan L, Liu JG, Zhao J, Brundell E, Daneholt B, et al. (2000) The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 5:73-83.
24. Yang F, De La Fuente R, Leu NA, Baumann C, McLaughlin KJ, et al. (2006) Mouse SYCP2 is required for synaptonemal complex assembly and chromosomal synapsis during male meiosis. J Cell Biol 173:497-507.
25. de Vries FA, de Boer E, van den Bosch M, Baarends WM, Ooms M, et al. (2005) Mouse Sycpl functions in synaptonemal complex assembly, meiotic recombination, and XY body formation. Genes Dev 19:1376-1389.
26. Hamer G, Wang H, Bolcun-Filas E, Cooke HJ, Benavente R, et al. (2008) Progression of meiotic recombination requires structural maturation of the central element of the synaptonemal complex. J Cell Sci 121:2445-2451.
27. Weiner BM, Kleckner N (1994) Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast. Cell 77:977-991.
28. Baudat F, Manova K, Yuen JP, Jasin M, Keeney S (2000) Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spol 1. Mol Cell 6:989-998.
29. Loidl J, Klein F, Scherthan H (1994) Homologous pairing is reduced but not abolished in asynaptic mutants of yeast. J Cell Biol 125:1191-1200.
30. Celerin M, Merino ST, Stone JE, Menzie AM, Zolan ME (2000) Multiple roles of Spol 1 in meiotic chromosome behavior. EMBO J 19:2739-2750.
31. Dernburg AF, McDonald K, Moulder G, Barstead R, Dresser M, et al. (1998) Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis. Cell 94:387-398.
32. McKim KS, Green-Marroquin BL, Sekelsky JJ, Chin G, Steinberg C, et al. (1998) Meiotic synapsis in the absence of recombination. Science 279:876-878.
33. Nagasawa H, Brogan JR, Peng Y, Little JB, Bedford JS (2010) Some unsolved problems and unresolved issues in radiation cytogenetics:a review and new data on roles of homologous recombination and non-homologous end joining. Mutat Res 701:12-22.
34. Baudat F, Keeney S (2001) Meiotic recombination:Making and breaking go hand in hand. Curr Biol 11:R45-48.
35. Moens PB, Marcon E, Shore JS, Kochakpour N, Spyropoulos B (2007) Initiation and resolution of interhomolog connections:crossover and non-crossover sites along mouse synaptonemal complexes. J Cell Sci 120:1017-1027.
36. Vasquez KM, Marburger K, Intody Z, Wilson JH (2001) Manipulating the mammalian genome by homologous recombination. Proc Natl Acad Sci U S A 98:8403-8410.
37. Berchowitz LE, Copenhaver GP (2010) Genetic interference:don't stand so close to me. Curr Genomics 11:91-102.
38. de los Santos T, Hunter N, Lee C, Larkin B, Loidl J, et al. (2003) The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. Genetics 164:81-94.
39. Argueso JL, Wanat J, Gemici Z, Alani E (2004) Competing crossover pathways act during meiosis in Saccharomyces cerevisiae. Genetics 168:1805-1816.
40. Chen SY, Tsubouchi T, Rockmill B, Sandler JS, Richards DR, et al. (2008) Global analysis of the meiotic crossover landscape. Dev Cell 15:401-415.
41. Higgins JD, Armstrong SJ, Franklin FC, Jones GH (2004) The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination:evidence for two classes of recombination in Arabidopsis. Genes Dev 18:2557-2570.
42. Copenhaver GP, Housworth EA, Stahl FW (2002) Crossover interference in Arabidopsis. Genetics 160:1631-1639.
43. Berchowitz LE, Francis KE, Bey AL, Copenhaver GP (2007) The role of AtMUS81 in interference-insensitive crossovers in A. thaliana. PLoS Genet 3:e132.
44. Higgins JD, Buckling EF, Franklin FC, Jones GH (2008) Expression and functional analysis of AtMUS81 in Arabidopsis meiosis reveals a role in the second pathway of crossing-over. Plant J 54:152-162.
45. Getz TJ, Banse SA, Young LS, Banse AV, Swanson J, et al. (2008) Reduced mismatch repair of heteroduplexes reveals "non"-interfering crossing over in wild-type Saccharomyces cerevisiae. Genetics 178:1251-1269.
46. Novak JE, Ross-Macdonald PB, Roeder GS (2001) The budding yeast Msh4 protein functions in chromosome synapsis and the regulation of crossover distribution. Genetics 158:1013-1025.
47. Conrad MN, Dominguez AM, Dresser ME (1997) Ndjlp, a meiotic telomere protein required for normal chromosome synapsis and segregation in yeast. Science 276:1252-1255.
48. Ohta K, Wu TC, Lichten M, Shibata T (1999) Competitive inactivation of a double-strand DNA break site involves parallel suppression of meiosis-induced changes in chromatin configuration. Nucleic Acids Res 27:2175-2180.
49. Wu TC, Lichten M (1995) Factors that affect the location and frequency of meiosis-induced double-strand breaks in Saccharomyces cerevisiae. Genetics 140:55-66.
50. Baudat F, de Massy B (2007) Regulating double-stranded DNA break repair towards crossover or non-crossover during mammalian meiosis. Chromosome Res 15:565-577.
51. Holloway JK, Booth J, Edelmann W, McGowan CH, Cohen PE (2008) MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. PLoS Genet 4: e1000186.
52. Neyton S, Lespinasse F, Moens PB, Paul R, Gaudray P, et al. (2004) Association between MSH4 (MutS homologue 4) and the DNA strand-exchange RAD51 and DMC1 proteins during mammalian meiosis. Mol Hum Reprod 10:917-924.
53. de Boer E, Stam P, Dietrich AJ, Pastink A, Heyting C (2006) Two levels of interference in mouse meiotic recombination. Proc Natl Acad Sci U S A 103:9607-9612.
54. de Boer E, Dietrich AJ, Hoog C, Stam P, Heyting C (2007) Meiotic interference among MLH1 foci requires neither an intact axial element structure nor full synapsis. J Cell Sci 120:731-736.
55. Buard J, de Massy B (2007) Playing hide and seek with mammalian meiotic crossover hotspots. Trends Genet 23:301-309.
56. Mezard C (2006) Meiotic recombination hotspots in plants. Biochem Soc Trans 34:531-534.
57. Pryce DW, McFarlane RJ (2009) The meiotic recombination hotspots of Schizosaccharomyces pombe. Genome Dyn 5:1-13.
58. Myers S, Bottolo L, Freeman C, McVean G, Donnelly P (2005) A fine-scale map of recombination rates and hotspots across the human genome. Science 310:321-324.
59. Berchowitz LE, Hanlon SE, Lieb JD, Copenhaver GP (2009) A positive but complex association between meiotic double-strand break hotspots and open chromatin in Saccharomyces cerevisiae. Genome Res 19:2245-2257.
60. Ohta K, Shibata T, Nicolas A (1994) Changes in chromatin structure at recombination initiation sites during yeast meiosis. EMBO J 13:5754-5763.
61. Wu TC, Lichten M (1994) Meiosis-induced double-strand break sites determined by yeast chromatin structure. Science 263:515-518.
62. Reddy KC, Villeneuve AM (2004) C. elegans HIM-17 links chromatin modification and competence for initiation of meiotic recombination. Cell 118:439-452.
63. Mets DG, Meyer BJ (2009) Condensins regulate meiotic DNA break distribution, thus crossover frequency, by controlling chromosome structure. Cell 139:73-86.
64. Tsai CJ, Mets DG, Albrecht MR, Nix P, Chan A, et al. (2008) Meiotic crossover number and distribution are regulated by a dosage compensation protein that resembles a condensin subunit. Genes Dev 22:194-211.
65. Goodyer W, Kaitna S, Couteau F, Ward JD, Boulton SJ, et al. (2008) HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis. Dev Cell 14: 263-274.
66. Kumar R, Bourbon HM, de Massy B (2010) Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice. Genes Dev 24:1266-1280.
67. Kleckner N (2006) Chiasma formation:chromatin/axis interplay and the role(s) of the synaptonemal complex. Chromosoma 115:175-194.
68. Myers S, Freeman C, Auton A, Donnelly P, McVean G (2008) A common sequence motif associated with recombination hot spots and genome instability in humans. Nat Genet 40: 1124-1129.
69. Ptak SE, Hinds DA, Koehler K, Nickel B, Patil N, et al. (2005) Fine-scale recombination patterns differ between chimpanzees and humans. Nat Genet 37:429-434.
70. Winckler W, Myers SR, Richter DJ, Onofrio RC, McDonald GJ, et al. (2005) Comparison of fine-scale recombination rates in humans and chimpanzees. Science 308:107-111.
71. Evans DM, Cardon LR (2005) A comparison of linkage disequilibrium patterns and estimated population recombination rates across multiple populations. Am J Hum Genet 76:681-687.
72. Cheung VG, Burdick JT, Hirschmann D, Morley M (2007) Polymorphic variation in human meiotic recombination. Am J Hum Genet 80:526-530.
73. Coop G, Wen X, Ober C, Pritchard JK, Przeworski M (2008) High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans. Science 319:1395-1398.
74. Wagner CR, Kuervers L, Baillie DL, Yanowitz JL (2010) xnd-1 regulates the global recombination landscape in Caenorhabditis elegans. Nature 467:839-843.
75. Borde V, Robine N, Lin W, Bonfils S, Geli V, et al. (2009) Histone H3 lysine 4 trimethylation marks meiotic recombination initiation sites. EMBO J 28:99-111.
76. Buard J, Barthes P, Grey C, de Massy B (2009) Distinct histone modifications define initiation and repair of meiotic recombination in the mouse. EMBO J 28:2616-2624.
77. Sigurdsson MI, Smith AV, Bjornsson HT, Jonsson JJ (2009) HapMap methylation-associated SNPs, markers of germline DNA methylation, positively correlate with regional levels of human meiotic recombination. Genome Res 19:581-589.
78. Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, et al. (2010) PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327:836-840.
79. Wahls WP, Davidson MK (2012) New paradigms for conserved, multifactorial, cis-acting regulation of meiotic recombination. Nucleic Acids Res 40:9983-9989.
80. Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, et al. (2005) Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120:169-181.
81. Schneider R, Bannister AJ, Myers FA, Thome AW, Crane-Robinson C, et al. (2004) Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol 6:73-77.
82. Kniewel R, Keeney S (2009) Histone methylation sets the stage for meiotic DNA breaks. EMBO J 28:81-83.
83. Shinohara M, Oh SD, Hunter N, Shinohara A (2008) Crossover assurance and crossover interference are distinctly regulated by the ZMM proteins during yeast meiosis. Nat Genet 40: 299-309.
84. Hillers KJ, Villeneuve AM (2003) Chromosome-wide control of meiotic crossing over in C. elegans. Curr Biol 13:1641-1647.
85. Lim JG, Stine RR, Yanowitz JL (2008) Domain-specific regulation of recombination in Caenorhabditis elegans in response to temperature, age and sex. Genetics 180:715-726.
86. Martini E, Diaz RL, Hunter N, Keeney S (2006) Crossover homeostasis in yeast meiosis. Cell 126:285-295.
87. Youds JL, Mets DG, McIlwraith MJ, Martin JS, Ward JD, et al. (2010) RTEL-1 enforces meiotic crossover interference and homeostasis. Science 327:1254-1258.
88. Joshi N, Barot A, Jamison C, Borner GV (2009) Pch2 links chromosome axis remodeling at future crossover sites and crossover distribution during yeast meiosis. PLoS Genet 5: e1000557.
89. King JS, Mortimer RK (1990) A polymerization model of chiasma interference and corresponding computer simulation. Genetics 126:1127-1138.
90. Kleckner N, Zickler D, Jones GH, Dekker J, Padmore R, et al. (2004) A mechanical basis for chromosome function. Proc Natl Acad Sci U S A 101:12592-12597.
91. Lynn A, Koehler KE, Judis L, Chan ER, Cherry JP, et al. (2002) Covariation of synaptonemal complex length and mammalian meiotic exchange rates. Science 296:2222-2225.
92. Petkov PM, Broman KW, Szatkiewicz JP, Paigen K (2007) Crossover interference underlies sex differences in recombination rates. Trends Genet 23:539-542.
93. Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428:145-150.
94. Hassold T, Jacobs PA, Leppert M, Sheldon M (1987) Cytogenetic and molecular studies of trisomy 13. J Med Genet 24:725-732.
95. Lamb NE, Feingold E, Savage A, Avramopoulos D, Freeman S, et al. (1997) Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21. Hum Mol Genet 6:1391-1399.
96. Thomas NS, Hassold TJ (2003) Aberrant recombination and the origin of Klinefelter syndrome. Hum Reprod Update 9:309-317.
97. Koehler KE, Hassold TJ (1998) Human aneuploidy:lessons from achiasmate segregation in Drosophila melanogaster. Ann Hum Genet 62:467-479.
98. Hassold T, Hunt P (2001) To err (meiotically) is human:the genesis of human aneuploidy. Nat Rev Genet 2:280-291.
99. Angell RR, Xian J, Keith J, Ledger W, Baird DT (1994) First meiotic division abnormalities in human oocytes:mechanism of trisomy formation. Cytogenet Cell Genet 65:194-202.
100. Hulten M, Eliasson R, Tillinger KG (1970) Low chiasma count and other meiotic irregularities in two infertile 46, XY men with spermatogenic arrest. Hereditas 65:285-290.
101. Gonsalves J, Sun F, Schlegel PN, Turek PJ, Hopps CV, et al. (2004) Defective recombination in infertile men. Hum Mol Genet 13:2875-2883.
102. Ma S, Ferguson KA, Arsovska S, Moens P, Chow V (2006) Reduced recombination associated with the production of aneuploid sperm in an infertile man:a case report. Hum Reprod 21:980-985.
103. Ferguson KA, Wong EC, Chow V, Nigro M, Ma S (2007) Abnormal meiotic recombination in infertile men and its association with sperm aneuploidy. Hum Mol Genet 16:2870-2879.
104. Savage AR, Petersen MB, Pettay D, Taft L, Allran K, et al. (1998) Elucidating the mechanisms of paternal non-disjunction of chromosome 21 in humans. Hum Mol Genet 7: 1221-1227.
105. Hassold TJ, Sherman SL, Pettay D, Page DC, Jacobs PA (1991) XY chromosome nondisjunction in man is associated with diminished recombination in the pseudoautosomal region. Am J Hum Genet 49:253-260.
106. Miyamoto T, Hasuike S, Yogev L, Maduro MR, Ishikawa M, et al. (2003) Azoospermia in patients heterozygous for a mutation in SYCP3. Lancet 362:1714-1719.
107. Palermo G, Joris H, Devroey P, Van Steirteghem AC (1992) Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 340:17-18.
108. Rudak E, Jacobs PA, Yanagimachi R (1978) Direct analysis of the chromosome constitution of human spermatozoa. Nature 274:911-913.
109. Martin RH, Balkan W, Burns K, Rademaker AW, Lin CC, et al. (1983) The chromosome constitution of 1000 human spermatozoa. Hum Genet 63:305-309.
110. Brandriff B, Gordon L, Ashworth L, Watchmaker G, Moore D,2nd, et al. (1985) Chromosomes of human sperm:variability among normal individuals. Hum Genet 70:18-24.
111. Mikamo K, Kamiguchi Y, Tateno H (1990) Spontaneous and in vitro radiation-induced chromosome aberrations in human spermatozoa:application of a new method. Prog Clin Biol Res 340B:447-456.
112. Templado C, Marquez C, Munne S, Colls P, Martorell MR, et al. (1996) An analysis of human sperm chromosome aneuploidy. Cytogenet Cell Genet 74:194-200.
113. Martin RH, Ko E, Chan K (1993) Detection of aneuploidy in human interphase spermatozoa by fluorescence in situ hybridization (FISH). Cytogenet Cell Genet 64:23-26.
114. Robbins WA, Segraves R, Pinkel D, Wyrobek AJ (1993) Detection of aneuploid human sperm by fluorescence in situ hybridization: evidence for a donor difference in frequency of sperm disomic for chromosomes 1 and Y. Am J Hum Genet 52:799-807.
115. Wyrobek AJ, Robbins WA, Mehraein Y, Pinkel D, Weier HU (1994) Detection of sex chromosomal aneuploidies X-X, Y-Y, and X-Y in human sperm using two-chromosome fluorescence in situ hybridization. Am J Med Genet 53:1-7.
116. Martin RH (1996) The risk of chromosomal abnormalities following ICSI. Hum Reprod 11: 924-925.
117. Downie SE, Flaherty SP, Matthews CD (1997) Detection of chromosomes and estimation of aneuploidy in human spermatozoa using fluorescence in-situ hybridization. Mol Hum Reprod 3:585-598.
118. Egozcue J, Blanco J, Vidal F (1997) Chromosome studies in human sperm nuclei using fluorescence in-situ hybridization (FISH). Hum Reprod Update 3:441-452.
119. Robbins WA, Meistrich ML, Moore D, Hagemeister FB, Weier HU, et al. (1997) Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm. Nat Genet 16:74-78.
120. Martin RH, Ernst S, Rademaker A, Barclay L, Ko E, et al. (1999) Analysis of sperm chromosome complements before, during, and after chemotherapy. Cancer Genet Cytogenet 108:133-136.
121. Hristova R, Ko E, Greene C, Rademaker A, Chernos J, et al. (2002) Chromosome abnormalities in sperm from infertile men with asthenoteratozoospermia. Biol Reprod 66: 1781-1783.
122. Shi Q, Spriggs E, Field LL, Rademaker A, Ko E, et al. (2002) Absence of age effect on meiotic recombination between human X and Y chromosomes. Am J Hum Genet 71:254-261.
123. Tiemann-Boege I, Calabrese P, Cochran DM, Sokol R, Arnheim N (2006) High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing. PLoS Genet 2:e70.
124. Baker SM, Plug AW, Prolla TA, Bronner CE, Harris AC, et al. (1996) Involvement of mouse Mlhl in DNA mismatch repair and meiotic crossing over. Nat Genet 13:336-342.
125. Anderson LK, Reeves A, Webb LM, Ashley T (1999) Distribution of crossing over on mouse synaptonemal complexes using immunofluorescent localization of MLH1 protein. Genetics 151:1569-1579.
126. Barlow AL, Hulten MA (1998) Crossing over analysis at pachytene in man. Eur J Hum Genet 6:350-358.
127. Tease C, Hartshorne G, Hulten M (2006) Altered patterns of meiotic recombination in human fetal oocytes with asynapsis and/or synaptonemal complex fragmentation at pachytene. Reprod Biomed Online 13:88-95.
128. Sun F, Oliver-Bonet M, Liehr T, Starke H, Ko E, et al. (2004) Human male recombination maps for individual chromosomes. Am J Hum Genet 74:521-531.
129. Sun F, Trpkov K, Rademaker A, Ko E, Martin RH (2005) Variation in meiotic recombination frequencies among human males. Hum Genet 116:172-178.
130. Sun F, Oliver-Bonet M, Liehr T, Starke H, Turek P, et al. (2006) Variation in MLH1 distribution in recombination maps for individual chromosomes from human males. Hum Mol Genet 15:2376-2391.
131. Oliver-Bonet M, Navarro J, Codina-Pascual M, Carrera M, Egozcue J, et al. (2001) Meiotic segregation analysis in a t(4;8) carrier:comparison of FISH methods on sperm chromosome metaphases and interphase sperm nuclei. Eur J Hum Genet 9:395-403.
132. Codina-Pascual M, Oliver-Bonet M, Navarro J, Campillo M, Garcia F, et al. (2005) Synapsis and meiotic recombination analyses:MLH1 focus in the XY pair as an indicator. Hum Reprod 20:2133-2139.
133. Benet J, Martin RH (1988) Sperm chromosome complements in a 47.XYY man. Hum Genet 78:313-315.
134. Martin RH, McInnes B, Rademaker AW (1999) Analysis of aneuploidy for chromosomes 13, 21, X and Y by multicolour fluorescence in situ hybridisation (FISH) in a 47,XYY male. Zygote 7:131-134.
135. Mercier S, Morel F, Roux C, Clavequin MC, Bresson JL (1996) Analysis of the sex chromosomal equipment in spermatozoa of a 47,XYY male using two-colour fluorescence in-situ hybridization. Mol Hum Reprod 2:485-488.
136. Chevret E, Rousseaux S, Monteil M, Usson Y, Cozzi J, et al. (1997) Meiotic behaviour of sex chromosomes investigated by three-colour FISH on 35,142 sperm nuclei from two 47,XYY males. Hum Genet 99:407-412.
137. Shi Q, Martin RH (2000) Multicolor fluorescence in situ hybridization analysis of meiotic chromosome segregation in a 47,XYY male and a review of the literature. Am J Med Genet 93:40-46.
138. Gonzalez-Merino E, Hans C, Abramowicz M, Englert Y, Emiliani S (2007) Aneuploidy study in sperm and preimplantation embryos from nonmosaic 47,XYY men. Fertil Steril 88: 600-606.
139. Ogawa S, Araki S, Araki Y, Ohno M, Sato I (2000) Chromosome analysis of human spermatozoa from an oligoasthenozoospermic carrier for a 13;14 Robertsonian translocation by their injection into mouse oocytes. Hum Reprod 15:1136-1139.
140. Rousseaux S, Chevret E (1995) In-vitro decondensation of human spermatozoa for fluorescence in-situ hybridization. Hum Reprod 10:2209-2213.
141. Blanco J, Egozcue J, Vidal F (2000) Interchromosomal effects for chromosome 21 in carriers of structural chromosome reorganizations determined by fluorescence in situ hybridization on sperm nuclei. Hum Genet 106:500-505.
142. Honda H, Miharu N, Samura O, He H, Ohama K (2000) Meiotic segregation analysis of a 14;21 Robertsonian translocation carrier by fluorescence in situ hybridization. Hum Genet 106:188-193.
143. Kirkpatrick G, Chow V, Ma S (2012) Meiotic recombination, synapsis, meiotic inactivation and sperm aneuploidy in a chromosome 1 inversion carrier. Reprod Biomed Online 24:91-100.
144. Frydman N, Romana S, Le Lorc'h M, Vekemans M, Frydman R, et al. (2001) Assisting reproduction of infertile men carrying a Robertsonian translocation. Hum Reprod 16:2274-2277.
145. Anahory T, Hamamah S, Andreo B, Hedon B, Claustres M, et al. (2005) Sperm segregation analysis of a (13;22) Robertsonian translocation carrier by FISH:a comparison of locus-specific probe and whole chromosome painting. Hum Reprod 20:1850-1854.
146. Moradkhani K, Puechberty J, Bhatt S, Vago P, Janny L, et al. (2006) Meiotic segregation of rare Robertsonian translocations:sperm analysis of three t(14q;22q) cases. Hum Reprod 21: 1166-1171.
147. Chen Y, Huang J, Liu P, Qiao J (2007) Analysis of meiotic segregation patterns and interchromosomal effects in sperm from six males with Robertsonian translocations. J Assist Reprod Genet 24:406-411.
148. Nishikawa N, Sato T, Suzumori N, Sonta S, Suzumori K (2008) Meiotic segregation analysis in male translocation carriers by using fluorescent in situ hybridization. Int J Androl 31:60-66.
149. Boue A, Gallano P (1984) A collaborative study of the segregation of inherited chromosome structural rearrangements in 1356 prenatal diagnoses. Prenat Diagn 4 Spec No:45-67.
150. Cifuentes P, Navarro J, Blanco J, Vidal F, Miguez L, et al. (1999) Cytogenetic analysis of sperm chromosomes and sperm nuclei in a male heterozygous for a reciprocal translocation t(5;7)(q21;q32) by in situ hybridisation. Eur J Hum Genet 7:231-238.
151. Hulten M, Goldman A (1993) The relationship between meiotic chromosome pairing and chiasma formation. Hum Genet 91:300.
152. Estop AM, Cieply KM, Wakim A, Feingold E (1998) Meiotic products of two reciprocal translocations studied by multicolor fluorescence in situ hybridization. Cytogenet Cell Genet 83:193-198.
153. Oliver-Bonet M, Benet J, Sun F, Navarro J, Abad C, et al. (2005) Meiotic studies in two human reciprocal translocations and their association with spermatogenic failure. Hum Reprod 20:683-688.
154. Morel F, Douet-Guilbert N, Roux C, Tripogney C, Le Bris MJ, et al. (2004) Meiotic segregation of at(7;8)(q11.21;cen) translocation in two carrier brothers. Fertil Steril 81:682-685.
155. Vozdova M, Oracova E, Horinova V, Rubes J (2008) Sperm fluorescence in situ hybridization study of meiotic segregation and an interchromosomal effect in carriers of t(11;18). Hum Reprod 23:581-588.
156. Cora T, Acar H, Kaynak M (2002) Molecular cytogenetic detection of meiotic segregation patterns in sperm nuclei of carriers of 46,XY,t(15;17)(q21; q25). J Androl 23:793-798.
157. Pettenati MJ, Rao PN, Phelan MC, Grass F, Rao KW, et al. (1995) Paracentric inversions in humans:a review of 446 paracentric inversions with presentation of 120 new cases. Am J Med Genet 55:171-187.
158. Martin RH (1999) Sperm chromosome analysis in a man heterozygous for a paracentric inversion of chromosome 14 (q24.1q32.1). Am J Hum Genet 64:1480-1484.
159. Anton E, Vidal F, Blanco J (2007) Role of sperm FISH studies in the genetic reproductive advice of structural reorganization carriers. Hum Reprod 22:2088-2092.
160. Chantot-Bastaraud S, Ravel C, Berthaut I, McElreavey K, Bouchard P, et al. (2007) Sperm-FISH analysis in a pericentric chromosome 1 inversion,46,XY,inv(1)(p22q42), associated with infertility. Mol Hum Reprod 13:55-59.
161. Morel F, Laudier B, Guerif F, Couet ML, Royere D, et al. (2007) Meiotic segregation analysis in spermatozoa of pericentric inversion carriers using fluorescence in-situ hybridization. Hum Reprod 22:136-141.
162. Daniel A, Hook EB, Wulf G (1989) Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements:data from United States and Canadian laboratories. Am J Med Genet 33:14-53.
163. Hopps CV, Mielnik A, Goldstein M, Palermo GD, Rosenwaks Z, et al. (2003) Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Hum Reprod 18:1660-1665.
164. Wieacker P, Jakubiczka S (1997) Genetic causes of male infertility. Andrologia 29:63-69.
165. Aboulghar H, Aboulghar M, Mansour R, Serour G, Amin Y, et al. (2001) A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection. Fertil Steril 76:249-253.
166. Marcon E, Moens P (2003) MLHlp and MLH3p localize to precociously induced chiasmata of okadaic-acid-treated mouse spermatocytes. Genetics 165:2283-2287.
167. Oliver-Bonet M, Ko E, Martin RH (2005) Male infertility in reciprocal translocation carriers: the sex body affair. Cytogenet Genome Res 111:343-346.
168. Sun F, Greene C, Turek PJ, Ko E, Rademaker A, et al. (2005) Immunofluorescent synaptonemal complex analysis in azoospermic men. Cytogenet Genome Res 111:366-370.
169. Gabriel-Robez O, Ratomponirina C, Dutrillaux B, Carre-Pigeon F, Rumpler Y (1986) Meiotic association between the XY chromosomes and the autosomal quadrivalent of a reciprocal translocation in two infertile men,46,XY,t(19;22) and 46,XY,t(17;21). Cytogenet Cell Genet 43:154-160.
170. Genschel J, Bazemore LR, Modrich P (2002) Human exonuclease I is required for 5' and 3' mismatch repair. J Biol Chem 277:13302-13311.
171. Kogo H, Kowa-Sugiyama H, Yamada K, Bolor H, Tsutsumi M, et al. (2010) Screening of genes involved in chromosome segregation during meiosis I:toward the identification of genes responsible for infertility in humans. J Hum Genet 55:293-299.
172. Sanderson ML, Hassold TJ, Carrell DT (2008) Proteins involved in meiotic recombination:a role in male infertility? Syst Biol Reprod Med 54:57-74.
173. Tempest HG (2011) Meiotic recombination errors, the origin of sperm aneuploidy and clinical recommendations. Syst Biol Reprod Med 57:93-101.
174. Ko E, Martin RH (2009) Immunofluorescence analysis of human spermatocytes. Methods Mol Biol 558:401-418.
175. Matzuk MM, Lamb DJ (2008) The biology of infertility:research advances and clinical challenges. Nat Med 14:1197-1213.
176. Christensen GL, Ivanov IP, Atkins JF, Mielnik A, Schlegel PN, et al. (2005) Screening the SPO11 and EIF5A2 genes in a population of infertile men. Fertil Steril 84:758-760.
177. Yuan L, Liu JG, Hoja MR, Wilbertz J, Nordqvist K, et al. (2002) Female germ cell aneuploidy and embryo death in mice lacking the meiosis-specific protein SCP3. Science 296: 1115-1118.
178. Thomas M, Lieberman J, Lal A (2010) Desperately seeking microRNA targets. Nat Struct Mol Biol 17:1169-1174.
179. Zhang B, Wang Q, Pan X (2007) MicroRNAs and their regulatory roles in animals and plants. J Cell Physiol 210:279-289.
180. DeSano JT, Xu L (2009) MicroRNA regulation of cancer stem cells and therapeutic implications. AAPS J 11:682-692.
181. Papaioannou MD, Nef S (2010) microRNAs in the testis:building up male fertility. J Androl 31:26-33.
182. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294:853-858.
183. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15-20.
184. Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, et al. (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442:203-207.
185. Girard A, Sachidanandam R, Hannon GJ, Carmell MA (2006) A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442:199-202.
186. Grivna ST, Beyret E, Wang Z, Lin H (2006) A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 20:1709-1714.
187. Klattenhoff C, Theurkauf W (2008) Biogenesis and germline functions of piRNAs. Development 135:3-9.
188. Braun RE (1998) Post-transcriptional control of gene expression during spermatogenesis. Semin Cell Dev Biol 9:483-489.
189. Kleene KC (1993) Multiple controls over the efficiency of translation of the mRNAs encoding transition proteins, protamines, and the mitochondrial capsule selenoprotein in late spermatids in mice. Dev Biol 159:720-731.
190. Yang J, Chennathukuzhi V, Miki K, O'Brien DA, Hecht NB (2003) Mouse testis brain RNA-binding protein/translin selectively binds to the messenger RNA of the fibrous sheath protein glyceraldehyde 3-phosphate dehydrogenase-S and suppresses its translation in vitro. Biol Reprod 68:853-859.
191. Hake LE, Mendez R, Richter JD (1998) Specificity of RNA binding by CPEB:requirement for RNA recognition motifs and a novel zinc finger. Mol Cell Biol 18:685-693.
192. Wu XQ, Xu L, Hecht NB (1998) Dimerization of the testis brain RNA-binding protein (translin) is mediated through its C-terminus and is required for DNA-and RNA-binding. Nucleic Acids Res 26:1675-1680.
193. Morales CR, Wu XQ, Hecht NB (1998) The DNA/RNA-binding protein, TB-RBP, moves from the nucleus to the cytoplasm and through intercellular bridges in male germ cells. Dev Biol 201:113-123.
194. Chennathukuzhi V, Stein JM, Abel T, Donlon S, Yang S, et al. (2003) Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes. Mol Cell Biol 23:6419-6434.
195. Giorgini F, Davies HG, Braun RE (2002) Translational repression by MSY4 inhibits spermatid differentiation in mice. Development 129:3669-3679.
196. Steger K (2001) Haploid spermatids exhibit translationally repressed mRNAs. Anat Embryol (Berl) 203:323-334.
197. Kwon YK, Hecht NB (1991) Cytoplasmic protein binding to highly conserved sequences in the 31 untranslated region of mouse protamine 2 mRNA, a translationally regulated transcript of male germ cells. Proc Natl Acad Sci U S A 88:3584-3588.
198. Carthew RW, Sontheimer EJ (2009) Origins and Mechanisms of miRNAs and siRNAs. Cell 136:642-655.
199. Ghildiyal M, Zamore PD (2009) Small silencing RNAs:an expanding universe. Nat Rev Genet 10:94-108.
200. Aravin AA, Lagos-Quintana M, Yalcin A, Zavolan M, Marks D, et al. (2003) The small RNA profile during Drosophila melanogaster development. Dev Cell 5:337-350.
201. Lai EC, Tomancak P, Williams RW, Rubin GM (2003) Computational identification of Drosophila microRNA genes. Genome Biol 4:R42.
202. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, et al. (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769-773.
203. Lee RC, Ambros V (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294:862-864.
204. Kim CH, Kim SR, Cheon YP, Kim SH, Chae HD, et al. (2009) Minimal stimulation using gonadotropin-releasing hormone (GnRH) antagonist and recombinant human follicle- stimulating hormone versus GnRH antagonist multiple-dose protocol in low responders undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril 92: 2082-2084.
205. Han J, Lee Y, Yeom KH, Kim YK, Jin H, et al. (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18:3016-3027.
206. Landthaler M, Yalcin A, Tuschl T (2004) The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol 14: 2162-2167.
207. Yi R, Qin Y, Macara IG, Cullen BR (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17:3011-3016.
208. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, et al. (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15:185-197.
209. Pillai RS, Artus CG, Filipowicz W (2004) Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis. RNA 10:1518-1525.
210. Su H, Trombly MI, Chen J, Wang X (2009) Essential and overlapping functions for mammalian Argonautes in microRNA silencing. Genes Dev 23:304-317.
211. Olsen PH, Ambros V (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 216:671-680.
212. Petersen CP, Bordeleau ME, Pelletier J, Sharp PA (2006) Short RNAs repress translation after initiation in mammalian cells. Mol Cell 21:533-542.
213. Humphreys DT, Westman BJ, Martin DI, Preiss T (2005) MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc Natl Acad Sci U S A 102:16961-16966.
214. Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, et al. (2005) Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309:1573-1576.
215. Wang B, Love TM, Call ME, Doench JG, Novina CD (2006) Recapitulation of short RNA-directed translational gene silencing in vitro. Mol Cell 22:553-560.
216. Mathonnet G, Fabian MR, Svitkin YV, Parsyan A, Huck L, et al. (2007) MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317:1764-1767.
217. Nottrott S, Simard MJ, Richter JD (2006) Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat Struct Mol Biol 13:1108-1114.
218. Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, et al. (2005) Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122:553-563.
219. Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, et al. (2006) Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312:75-79.
220. Buchold GM, Coarfa C, Kim J, Milosavljevic A, Gunaratne PH, et al. (2010) Analysis of microRNA expression in the prepubertal testis. PLoS One 5:e15317.
221. Hayashi K, Chuva de Sousa Lopes SM, Kaneda M, Tang F, Hajkova P, et al. (2008) MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS One 3:e1738.
222. Guo X, Wu Y, Hartley RS (2009) MicroRNA-125a represses cell growth by targeting HuR in breast cancer. RNA Biol 6:575-583.
223. Zhong X, Li N, Liang S, Huang Q, Coukos G, et al. (2010) Identification of microRNAs regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells. J Biol Chem 285:41961-41971.
224. Yan N, Lu Y, Sun H, Qiu W, Tao D, et al. (2009) Microarray profiling of microRNAs expressed in testis tissues of developing primates. J Assist Reprod Genet 26:179-186.
225. Luo L, Ye L, Liu G, Shao G, Zheng R, et al. (2010) Microarray-based approach identifies differentially expressed microRNAs in porcine sexually immature and mature testes. PLoS One 5:e11744.
226. Liming S, Pathak S (1981) Gametogenesis in a male Indian muntjac x Chinese muntjac hybrid. Cytogenet Cell Genet 30:152-156.
227. Schmidtke J, Brennecke H, Schmid M, Neitzel H, Sperling K (1981) Evolution of muntjac DNA. Chromosoma 84:187-193.
228. Yu LC, Lowensteiner D, Wong EF, Sawada I, Mazrimas J, et al. (1986) Localization and characterization of recombinant DNA clones derived from the highly repetitive DNA sequences in the Indian muntjac cells:their presence in the Chinese muntjac. Chromosoma 93:521-528.
229. Li YC, Lee C, Sanoudou D, Hseu TH, Li SY, et al. (2000) Interstitial colocalization of two cervid satellite DNAs involved in the genesis of the Indian muntjac karyotype. Chromosome Res 8:363-373.
230. Lin CC, Chiang PY, Hsieh LJ, Liao SJ, Chao MC, et al. (2004) Cloning, characterization and physical mapping of three cervid satellite DNA families in the genome of the Formosan muntjac (Muntiacus reevesi micrurus). Cytogenet Genome Res 105:100-106.
231. Liming S, Yingying Y, Xingsheng D (1980) Comparative cytogenetic studies on the red muntjac, Chinese muntjac, and their F1 hybrids. Cytogenet Cell Genet 26:22-27.
232. Yang F, Carter NP, Shi L, Ferguson-Smith MA (1995) A comparative study of karyotypes of muntjacs by chromosome painting. Chromosoma 103:642-652.
233. Fronicke L, Chowdhary BP, Scherthan H (1997) Segmental homology among cattle (Bos taurus), Indian muntjac (Muntiacus muntjak vaginalis), and Chinese muntjac (M. reevesi) karyotypes. Cytogenet Cell Genet 77:223-227.
234. Chi JX, Huang L, Nie W, Wang J, Su B, et al. (2005) Defining the orientation of the tandem fusions that occurred during the evolution of Indian muntjac chromosomes by BAC mapping. Chromosoma 114:167-172.
235. Murmann AE, Mincheva A, Scheuermann MO, Gautier M, Yang F, et al. (2008) Comparative gene mapping in cattle, Indian muntjac, and Chinese muntjac by fluorescence in situ hybridization. Genetica 134:345-351.
236. Ma K, Shi LM (1988) [Comparative studies on synaptonemal complexes in spermatocytes of Chinese muntjac Muntiacus reevesi, black muntjac M. crinifrons and Indian muntjac M. muntjak]. Yi Chuan Xue Bao 15:282-289.
237. Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, et al. (2002) A high-resolution recombination map of the human genome. Nat Genet 31:241-247.
238. Sun F, Oliver-Bonet M, Liehr T, Starke H, Turek P, et al. (2006) Analysis of non-crossover bivalents in pachytene cells from 10 normal men. Hum Reprod 21:2335-2339.
239. Pigozzi MI (2001) Distribution of MLH1 foci on the synaptonemal complexes of chicken oocytes. Cytogenet Cell Genet 95:129-133.
240. Froenicke L, Anderson LK, Wienberg J, Ashley T (2002) Male mouse recombination maps for each autosome identified by chromosome painting. Am J Hum Genet 71:1353-1368.
241. Pardo-Manuel de Villena F, Sapienza C (2001) Recombination is proportional to the number of chromosome arms in mammals. Mamm Genome 12:318-322.
242. Jensen-Seaman MI, Furey TS, Payseur BA, Lu Y, Roskin KM, et al. (2004) Comparative recombination rates in the rat, mouse, and human genomes. Genome Res 14:528-538.
243. Coop G, Przeworski M (2007) An evolutionary view of human recombination. Nat Rev Genet 8:23-34.
244. Otto SP, Lenormand T (2002) Resolving the paradox of sex and recombination. Nat Rev Genet 3:252-261.
245. Shi Q, Martin RH (2000) Aneuploidy in human sperm:a review of the frequency and distribution of aneuploidy, effects of donor age and lifestyle factors. Cytogenet Cell Genet 90: 219-226.
246. Choo KH (1998) Why is the centromere so cold? Genome Res 8:81-82.
247. Borodin PM, Karamysheva TV, Rubtsov NB (2008) [Immunofluorescent analysis of meiotic recombination and interference in the domestic cat]. Tsitologiia 50:62-66.
248. Basheva EA, Bidau CJ, Borodin PM (2008) General pattern of meiotic recombination in male dogs estimated by MLH1 and RAD51 immunolocalization. Chromosome Res 16:709-719.
249. Scherthan H, Weich S, Schwegler H, Heyting C, Harle M, et al. (1996) Centromere and telomere movements during early meiotic prophase of mouse and man are associated with the onset of chromosome pairing. J Cell Biol 134:1109-1125.
250. Brown PW, Judis L, Chan ER, Schwartz S, Seftel A, et al. (2005) Meiotic synapsis proceeds from a limited number of subtelomeric sites in the human male. Am J Hum Genet 77:556-566.
251. Zickler D, Kleckner N (1999) Meiotic chromosomes:integrating structure and function. Annu Rev Genet 33:603-754.
252. Falque M, Mercier R, Mezard C, de Vienne D, Martin OC (2007) Patterns of recombination and MLH1 foci density along mouse chromosomes:modeling effects of interference and obligate chiasma. Genetics 176:1453-1467.
253. Borodin PM, Karamysheva TV, Belonogova NM, Torgasheva AA, Rubtsov NB, et al. (2008) Recombination map of the common shrew, Sorex araneus (Eulipotyphla, Mammalia). Genetics 178:621-632.
254. Broman KW, Murray JC, Sheffield VC, White RL, Weber JL (1998) Comprehensive human genetic maps:individual and sex-specific variation in recombination. Am J Hum Genet 63: 861-869.
255. Tease C, Hartshorne GM, Hulten MA (2002) Patterns of meiotic recombination in human fetal oocytes. Am J Hum Genet 70:1469-1479.
256. Tease C, Hulten MA (2004) Inter-sex variation in synaptonemal complex lengths largely determine the different recombination rates in male and female germ cells. Cytogenet Genome Res 107:208-215.
257. Laurie DA, Hulten MA (1985) Further studies on bivalent chiasma frequency in human males with normal karyotypes. Ann Hum Genet 49:189-201.
258. Hassold T, Judis L, Chan ER, Schwartz S, Seftel A, et al. (2004) Cytological studies of meiotic recombination in human males. Cytogenet Genome Res 107:249-255.
259. Chowdhury R, Bois PR, Feingold E, Sherman SL, Cheung VG (2009) Genetic analysis of variation in human meiotic recombination. PLoS Genet 5:e1000648.
260. Rasmussen SW, Holm PB (1984) The synaptonemal complex, recombination nodules and chiasmata in human spermatocytes. Symp Soc Exp Biol 38:271-292.
261. Vallente RU, Cheng EY, Hassold TJ (2006) The synaptonemal complex and meiotic recombination in humans:new approaches to old questions. Chromosoma 115:241-249.
262. Codina-Pascual M, Campillo M, Kraus J, Speicher MR, Egozcue J, et al. (2006) Crossover frequency and synaptonemal complex length:their variability and effects on human male meiosis. Mol Hum Reprod 12:123-133.
263. Hawley RS, Theurkauf WE (1993) Requiem for distributive segregation:achiasmate segregation in Drosophila females. Trends Genet 9:310-317.
264. Hulten M (1974) Chiasma distribution at diakinesis in the normal human male. Hereditas 76: 55-78.
265. Lipkin SM, Moens PB, Wang V, Lenzi M, Shanmugarajah D, et al. (2002) Meiotic arrest and aneuploidy in MLH3-deficient mice. Nat Genet 31:385-390.
266. Laurie DA, Hulten M, Jones GH (1981) Chiasma frequency and distribution in a sample of human males:chromosomes 1,2, and 9. Cytogenet Cell Genet 31:153-166.
267. Zenvirth D, Richler C, Bardhan A, Baudat F, Barzilai A, et al. (2003) Mammalian meiosis involves DNA double-strand breaks with 3'overhangs. Chromosoma 111:369-376.
268. Keeney S, Giroux CN, Kleckner N (1997) Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 88:375-384.
269. Shinohara A, Shinohara M (2004) Roles of RecA homologues Rad51 and Dmcl during meiotic recombination. Cytogenet Genome Res 107:201-207.
270. Sung P, Krejci L, Van Komen S, Sehorn MG (2003) Rad51 recombinase and recombination mediators. J Biol Chem 278:42729-42732.
271. Santucci-Darmanin S, Walpita D, Lespinasse F, Desnuelle C, Ashley T, et al. (2000) MSH4 acts in conjunction with MLH1 during mammalian meiosis. FASEB J 14:1539-1547.
272. Moens PB, Kolas NK, Tarsounas M, Marcon E, Cohen PE, et al. (2002) The time course and chromosomal localization of recombination-related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA-DNA interactions without reciprocal recombination. J Cell Sci 115:1611-1622.
273. Tesse S, Storlazzi A, Kleckner N, Gargano S, Zickler D (2003) Localization and roles of Ski8p protein in Sordaria meiosis and delineation of three mechanistically distinct steps of meiotic homolog juxtaposition. Proc Natl Acad Sci U S A 100:12865-12870.
274. Storlazzi A, Tesse S, Gargano S, James F, Kleckner N, et al. (2003) Meiotic double-strand breaks at the interface of chromosome movement, chromosome remodeling, and reductional division. Genes Dev 17:2675-2687.
275. McKim KS, Hayashi-Hagihara A (1998) mei-W68 in Drosophila melanogaster encodes a Spoll homolog:evidence that the mechanism for initiating meiotic recombination is conserved. Genes Dev 12:2932-2942.
276. Plug AW, Peters AH, Keegan KS, Hoekstra MF, de Boer P, et al. (1998) Changes in protein composition of meiotic nodules during mammalian meiosis. J Cell Sci 111 (Pt 4):413-423.
277. Loidl J (1994) Cytological aspects of meiotic recombination. Experientia 50:285-294.
278. Kleckner N, Storlazzi A, Zickler D (2003) Coordinate variation in meiotic pachytene SC length and total crossover/chiasma frequency under conditions of constant DNA length. Trends Genet 19:623-628.
279. Solari AJ (1970) The behaviour of chromosomal axes during diplotene in mouse spermatocytes. Chromosoma 31:217-230.
280. Solari AJ, Tres LL (1970) The three-dimensional reconstruction of the XY chromosomal pair in human spermatocytes. J Cell Biol 45:43-53.
281. Tres LL (1975) Nucleolar RNA synthesis of meiotic prophase spermatocytes in the human testis. Chromosoma 53:141-151.
282. Moses MJ (1977) Synaptonemal complex karyotyping in spermatocytes of the Chinese hamster (Cricetulus griseus). I. Morphology of the autosomal complement in spread preparations. Chromosoma 60:99-125.
283. Carpenter AT (1975) Electron microscopy of meiosis in Drosophila melanogaster females. I. Structure, arrangement, and temporal change of the synaptonemal complex in wild-type. Chromosoma 51:157-182.
284. Sandovici I, Kassovska-Bratinova S, Vaughan JE, Stewart R, Leppert M, et al. (2006) Human imprinted chromosomal regions are historical hot-spots of recombination. PLoS Genet2:e101.
285. Myers S, Spencer CC, Auton A, Bottolo L, Freeman C, et al. (2006) The distribution and causes of meiotic recombination in the human genome. Biochem Soc Trans 34:526-530.
286. Flanagan JM, Popendikyte V, Pozdniakovaite N, Sobolev M, Assadzadeh A, et al. (2006) Intra-and interindividual epigenetic variation in human germ cells. Am J Hum Genet 79:67-
287. Cheng AM, Byrom MW, Shelton J, Ford LP (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33:1290-1297.
288. Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, et al. (2005) Stem cell division is regulated by the microRNA pathway. Nature 435:974-978.
289. Maatouk DM, Loveland KL, McManus MT, Moore K, Harfe BD (2008) Dicerl is required for differentiation of the mouse male germline. Biol Reprod 79:696-703.
290. Barad O, Meiri E, Avniel A, Aharonov R, Barzilai A, et al. (2004) MicroRNA expression detected by oligonucleotide microarrays:system establishment and expression profiling in human tissues. Genome Res 14:2486-2494.
291. Yu Z, Raabe T, Hecht NB (2005) MicroRNA Mirn122a reduces expression of the posttranscriptionally regulated germ cell transition protein 2 (Tnp2) messenger RNA (mRNA) by mRNA cleavage. Biol Reprod 73:427-433.
292. Ro S, Park C, Sanders KM, McCarrey JR, Yan W (2007) Cloning and expression profiling of testis-expressed microRNAs. Dev Biol 311:592-602.
293. Yan N, Lu Y, Sun H, Tao D, Zhang S, et al. (2007) A microarray for microRNA profiling in mouse testis tissues. Reproduction 134:73-79.
294. Li G, Wu Z, Li X, Ning X, Li Y, et al. (2011) Biological role of microRNA-103 based on expression profile and target genes analysis in pigs. Mol Biol Rep 38:4777-4786.
295. Smorag L, Zheng Y, Nolte J, Zechner U, Engel W, et al. (2012) MicroRNA signature in various cell types of mouse spermatogenesis:Evidence for stage-specifically expressed miRNA-221,-203 and-34b-5p mediated spermatogenesis regulation. Biol Cell 104:677-692.
296. Lian C, Sun B, Niu S, Yang R, Liu B, et al. (2012) A comparative profile of the microRNA transcriptome in immature and mature porcine testes using Solexa deep sequencing. FEBS J.
297. Lian J, Tian H, Liu L, Zhang XS, Li WQ, et al. (2010) Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1. Cell Death Dis 1:e94.
298. Wu J, Bao J, Wang L, Hu Y, Xu C (2011) MicroRNA-184 downregulates nuclear receptor corepressor 2 in mouse spermatogenesis. BMC Dev Biol 11:64.
299. Bjork JK, Sandqvist A, Elsing AN, Kotaja N, Sistonen L (2010) miR-18, a member of Oncomir-1, targets heat shock transcription factor 2 in spermatogenesis. Development 137: 3177-3184.
300. Thomson T, Lin H (2009) The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annu Rev Cell Dev Biol 25:355-376.
301. Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T, et al. (2006) Characterization of the piRNA complex from rat testes. Science 313:363-367.
302. Lin H (2007) piRNAs in the germ line. Science 316:397.
303. Aravin AA, Sachidanandam R, Bourc'his D, Schaefer C, Pezic D, et al. (2008) A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 31:785-799.
304. Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316:744-747.
305. Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H (2002) Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene 21:3988-3999.
306. Carmell MA, Girard A, van de Kant HJ, Bourc'his D, Bestor TH, et al. (2007) MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell 12:503-514.
307. Sultan M, Schulz MH, Richard H, Magen A, Klingenhoff A, et al. (2008) A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science 321:956-960.
308. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5:621-628.
309. Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, et al. (2008) The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 320:1344-1349.
310. Wang Z, Gerstein M, Snyder M (2009) RNA-Seq:a revolutionary tool for transcriptomics. Nat Rev Genet 10:57-63.
311. Blow N (2009) Transcriptomics:The digital generation. Nature 458:239-242.
312. Li R, Yu C, Li Y, Lam TW, Yiu SM, et al. (2009) SOAP2:an improved ultrafast tool for short read alignment. Bioinformatics 25:1966-1967.
313. Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ (2008) miRBase:tools for microRNA genomics. Nucleic Acids Res 36:D154-158.
314. Griffiths-Jones S, Moxon S, Marshall M, Khanna A, Eddy SR, et al. (2005) Rfam:annotating non-coding RNAs in complete genomes. Nucleic Acids Res 33:D121-124.
315. Tarailo-Graovac M, Chen N (2009) Using RepeatMasker to identify repetitive elements in genomic sequences. Curr Protoc Bioinformatics Chapter 4:Unit 4 10.
316. Fujita PA, Rhead B, Zweig AS, Hinrichs AS, Karolchik D, et al. (2011) The UCSC Genome Browser database:update 2011. Nucleic Acids Res 39:D876-882.
317. Betel D, Wilson M, Gabow A, Marks DS, Sander C (2008) The microRNA.org resource: targets and expression. Nucleic Acids Res 36:D149-153.
318. Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M (2010) KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res 38: D355-360.
319. Reiss HE (1986) Population study of causes, treatment and outcome of infertility. Br Med J (Clin Res Ed)292:761.
320. Meng F, Hackenberg M, Li Z, Yan J, Chen T (2012) Discovery of novel microRNAs in rat kidney using next generation sequencing and microarray validation. PLoS One 7:e34394.
321. Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, et al. (2004) An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A 101:9740-9744.
322. Fabre F, Chan A, Heyer WD, Gangloff S (2002) Alternate pathways involving Sgs1/Top3, Mus81/Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication. Proc Natl Acad Sci U S A 99:16887-16892.
323. Moreau S, Ferguson JR, Symington LS (1999) The nuclease activity of Mrel 1 is required for meiosis but not for mating type switching, end joining, or telomere maintenance. Mol Cell Biol 19:556-566.
324. Paull TT, Gellert M (1999) Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mrel l/Rad50 complex. Genes Dev 13:1276-1288.
325. Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, et al. (2007) p53-mediated activation of miRNA34 candidate tumor-suppressor genes. CurrBiol 17:1298-1307.
326. Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, et al. (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26:745-752.
327. Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY (2007) MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res 67:8433-8438.
328. He L, He X, Lim LP, de Stanchina E, Xuan Z, et al. (2007) A microRNA component of the p53 tumour suppressor network. Nature 447:1130-1134.
329. Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, et al. (2007) Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 26:731-743.
330. Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, et al. (2007) Differential regulation of microRNAs by p53 revealed by massively parallel sequencing:miR-34a is a p53 target that induces apoptosis and Gl-arrest. Cell Cycle 6:1586-1593.
331. Tazawa H, Tsuchiya N, Izumiya M, Nakagama H (2007) Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A 104:15472-15477.
332. Cole KA, Attiyeh EF, Mosse YP, Laquaglia MJ, Diskin SJ, et al. (2008) A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene. Mol Cancer Res 6: 735-742.
333. Concepcion CP, Han YC, Mu P, Bonetti C, Yao E, et al. (2012) Intact p53-dependent responses in miR-34-deficient mice. PLoS Genet 8:e1002797.
334. Liang X, Zhou D, Wei C, Luo H, Liu J, et al. (2012) MicroRNA-34c enhances murine male germ cell apoptosis through targeting ATF1. PLoS One 7:e33861.
335. Klemm DJ, Roesler WJ, Boras T, Colton LA, Felder K, et al. (1998) Insulin stimulates cAMP-response element binding protein activity in HepG2 and 3T3-L1 cell lines. J Biol Chem 273:917-923.
336. Bleckmann SC, Blendy JA, Rudolph D, Monaghan AP, Schmid W, et al. (2002) Activating transcription factor 1 and CREB are important for cell survival during early mouse development. Mol Cell Biol 22:1919-1925.
337. Jin XL, O'Neill C (2010) The presence and activation of two essential transcription factors (cAMP response element-binding protein and cAMP-dependent transcription factor ATF1) in the two-cell mouse embryo. Biol Reprod 82:459-468.
338. Liu K, Cho YY, Yao K, Nadas J, Kim DJ, et al. (2011) Eriodictyol inhibits RSK2-ATF1 signaling and suppresses EGF-induced neoplastic cell transformation. J Biol Chem 286: 2057-2066.
339. Xie H, Lim B, Lodish HF (2009) MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity. Diabetes 58:1050-1057.
340. Yang GH, Wang F, Yu J, Wang XS, Yuan JY, et al. (2009) MicroRNAs are involved in erythroid differentiation control. J Cell Biochem 107:548-556.
341. Neilson JR, Zheng GX, Burge CB, Sharp PA (2007) Dynamic regulation of miRNA expression in ordered stages of cellular development. Genes Dev 21:578-589.
342. Wilfred BR, Wang WX, Nelson PT (2007) Energizing miRNA research:a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways. Mol Genet Metab 91:209-217.
343. Bannister SC, Tizard ML, Doran TJ, Sinclair AH, Smith CA (2009) Sexually dimorphic microRNA expression during chicken embryonic gonadal development. Biol Reprod 81: 165-176.
344. Zhai Q, Zhou L, Zhao C, Wan J, Yu Z, et al. (2012) Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma. Biochem Biophys Res Commun 419:621-626.
345. Houwing S, Kamminga LM, Berezikov E, Cronembold D, Girard A, et al. (2007) A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell 129: 69-82.
346. Beyret E, Liu N, Lin H (2012) piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism. Cell Res 22:1429-1439.
347. Watanabe T, Takeda A, Tsukiyama T, Mise K, Okuno T, et al. (2006) Identification and characterization of two novel classes of small RNAs in the mouse germline:retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes Dev 20:1732-1743.
348. Bartel DP (2004) MicroRNAs:genomics, biogenesis, mechanism, and function. Cell 116: 281-297.
349. Lin S, Cheung WK, Chen S, Lu G, Wang Z, et al. (2010) Computational identification and characterization of primate-specific microRNAs in human genome. Comput Biol Chem 34: 232-241.
350. Li J, Liu Y, Dong D, Zhang Z (2010) Evolution of an X-linked primate-specific micro RNA cluster. Mol Biol Evol 27:671-683.
351. Song R, Ro S, Michaels JD, Park C, McCarrey JR, et al. (2009) Many X-linked microRNAs escape meiotic sex chromosome inactivation. Nat Genet 41:488-493.