Characterization and comparative profiling of ovarian microRNAs during ovine anestrus and the breeding season

BMC Genomics

Mingxing Chu¹  Ying Ge¹  Zhimin Yang¹  Jinxin Wang¹  Guiling Cao¹  Wenming Zhao³  Jiandong Wang²  Min Sun³  Qing Ma²  Xiaojun Liang²  Qiuyue Liu¹  Dongmei Tian³  Shuhui Song³  Jianning He¹  Ran Di¹ 

[1] Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, No. 2, Yuanmingyuan West Rd, Beijing, China;Research Center of Grass and Livestock, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan, Ningxia, China;Core Genomic Facility, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China

关键词: piRNA;    miRNA;    Ovary;    Anestrus;    Seasonal estrus;    Sheep;   

Others  :  1128457
DOI  :  10.1186/1471-2164-15-899

 received in 2014-07-30, accepted in 2014-10-08,  发布年份 2014

【 摘 要 】

Background

Seasonal estrus is a critical limiting factor of animal fecundity, and it involves changes in both ovarian biology and hormone secretion in different seasons. Previous studies indicate that two classes of small RNAs (miRNAs and piRNAs) play important regulatory roles in ovarian biology. To understand the roles of small RNA-mediated post-transcriptional regulation in ovine seasonal estrus, the variation in expression patterns of ovarian small RNAs during anestrus and the breeding season were analyzed using Solexa sequencing technology. In addition, reproductive hormone levels were determined during ovine anestrus and the breeding season.

Results

A total of 483 miRNAs (including 97 known, 369 conserved and 17 predicated novel miRNAs), which belong to 183 different miRNA families, were identified in ovaries of Tan sheep and Small Tail Han (STH) sheep. Compared with the three stages of the breeding season, 25 shared significantly differentially expressed (including 19 up- and six down-regulated) miRNAs were identified in ovine anestrus. KEGG Pathway analysis revealed that the target genes for some of the differentially expressed miRNAs were involved in reproductive hormone related pathways (e.g. steroid biosynthesis, androgen and estrogen metabolism and GnRH signaling pathway) as well as follicular/luteal development related pathways. Moreover, the expression of the differentially expressed miRNAs and most of their target genes were negatively correlated in the above pathways. Furthermore, the levels of estrogen, progesterone and LH in ovine anestrus were significantly lower than those in the breeding season. Combining the results of pathway enrichment analysis, expression of target genes and hormone measurement, we suggest that these differentially expressed miRNAs in anestrus might participate in attenuation of ovarian activity by regulating the above pathways. Besides miRNAs, a large and unexpectedly diverse set of piRNAs were also identified.

Conclusions

The miRNA profiles of ovine ovaries in anestrus were presented for the first time. The identification and characterization of miRNAs that are differentially expressed between ovine anestrus and the breeding season will help understanding of the role of miRNAs in the regulation of seasonal estrus, and provides candidates for determining miRNAs which could be potentially used to regulate ovine seasonal estrus.

【 授权许可】

   
2014 Di et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

【 参考文献 】

• [1]Tu YR: Sheep and Goat Breeds in China: Shanghai Scientific & Technology Publishers. 1989.
• [2]McBride D, Carre W, Sontakke SD, Hogg CO, Law A, Donadeu FX, Clinton M: Identification of miRNAs associated with the follicular-luteal transition in the ruminant ovary. Reproduct 2012, 144(2):221-233.
• [3]Ling YH, Ren CH, Guo XF, Xu LN, Huang YF, Luo JC, Zhang YH, Zhang XR, Zhang ZJ: Identification and characterization of microRNAs in the ovaries of multiple and uniparous goats (Capra hircus) during follicular phase. BMC Genomics 2014, 15(1):339. BioMed Central Full Text
• [4]Ji Z, Wang G, Xie Z, Zhang C, Wang J: Identification and characterization of microRNA in the dairy goat (Capra hircus) mammary gland by Solexa deep-sequencing technology. Mol Biol Rep 2012, 39(10):9361-9371.
• [5]Wu J, Zhu H, Song W, Li M, Liu C, Li N, Tang F, Mu H, Liao M, Li X, Guan W, Li X, Hua J: Identification of conservative microRNAs in Saanen dairy goat testis through deep sequencing. Reprod Domest Anim 2014, 49(1):32-40.
• [6]Liu Z, Xiao H, Li H, Zhao Y, Lai S, Yu X, Cai T, Du C, Zhang W, Li J: Identification of conserved and novel microRNAs in cashmere goat skin by deep sequencing. PLoS One 2012, 7(12):e50001.
• [7]Yuan C, Wang X, Geng R, He X, Qu L, Chen Y: Discovery of cashmere goat (Capra hircus) microRNAs in skin and hair follicles by Solexa sequencing. BMC Genomics 2013, 14:511. BioMed Central Full Text
• [8]Zhang XD, Zhang YH, Ling YH, Liu Y, Cao HG, Yin ZJ, Ding JP, Zhang XR: Characterization and differential expression of microRNAs in the ovaries of pregnant and non-pregnant goats (Capra hircus). BMC Genomics 2013, 14:157. BioMed Central Full Text
• [9]Zhang S, Zhao F, Wei C, Sheng X, Ren H, Xu L, Lu J, Liu J, Zhang L, Du L: Identification and characterization of the miRNA transcriptome of Ovis aries. PLoS One 2013, 8(3):e58905.
• [10]Otsuka M, Zheng M, Hayashi M, Lee JD, Yoshino O, Lin S, Han J: Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice. J Clin Invest 2008, 118(5):1944-1954.
• [11]Yao GD, Yin MM, Lian J, Tian H, Liu L, Li X, Sun F: MicroRNA-224 is involved in transforming growth factor-beta-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4. Mol Endocrinol 2010, 24(3):540-551.
• [12]Lin F, Li R, Pan ZX, Zhou B, Yu DB, Wang XG, Ma XS, Han J, Shen M, Liu HL: miR-26b promotes granulosa cell apoptosis by targeting ATM during follicular atresia in porcine ovary. PLoS One 2012, 7(6):e38640.
• [13]Grivna ST, Beyret E, Wang Z, Lin H: A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 2006, 20(13):1709-1714.
• [14]Grivna ST, Pyhtila B, Lin H: MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proc Natl Acad Sci U S A 2006, 103(36):13415-13420.
• [15]Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel DP, Kingston RE: Characterization of the piRNA complex from rat testes. Science 2006, 313(5785):363-367.
• [16]Malone CD, Brennecke J, Dus M, Stark A, McCombie WR, Sachidanandam R, Hannon GJ: Specialized piRNA pathways act in germline and somatic tissues of the drosophila ovary. Cell 2009, 137(3):522-535.
• [17]Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, Hodges E, Anger M, Sachidanandam R, Schultz RM, Hannon GJ: Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 2008, 453(7194):534-538.
• [18]Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, Chiba H, Kohara Y, Kono T, Nakano T, Surani MA, Sakaki Y, Sasaki H: Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 2008, 453(7194):539-543.
• [19]Yang CX, Du ZQ, Wright EC, Rothschild MF, Prather RS, Ross JW: Small RNA profile of the cumulus-oocyte complex and early embryos in the pig. Biol Reprod 2012, 87(5):117.
• [20]Li CJ, Vagin VV, Lee SH, Xu J, Ma SM, Xi HL, Seitz H, Horwich MD, Syrzycka M, Honda BM, Kittler ELW, Zapp ML, Klattenhoff C, Schulz N, Theurkauf WE, Weng ZP, Zamore PD: Collapse of germline piRNAs in the absence of argonaute3 reveals somatic piRNAs in flies. Cell 2009, 137(3):509-521.
• [21]Gerstl MP, Hackl M, Graf AB, Borth N, Grillari J: Prediction of transcribed PIWI-interacting RNAs from CHO RNAseq data. J Biotechnol 2013, 166(1–2):51-57.
• [22]Ding X, Guan H, Li H: Characterization of a piRNA binding protein Miwi in mouse oocytes. Theriogenol 2013, 79(4):610-615.
• [23]Hossain MM, Ghanem N, Hoelker M, Rings F, Phatsara C, Tholen E, Schellander K, Tesfaye D: Identification and characterization of miRNAs expressed in the bovine ovary. BMC Genomics 2009, 10:443. BioMed Central Full Text
• [24]Huang JM, Ju ZH, Li QL, Hou QL, Wang CF, Li JB, Li RL, Wang LL, Sun T, Hang SQ, Gao YD, Hou MH, Zhong JF: Solexa sequencing of novel and differentially expressed microRNAs in testicular and ovarian tissues in Holstein cattle. Int J Biol Sci 2011, 7(7):1016-1026.
• [25]Tripurani SK, Xiao CD, Salem M, Yao JB: Cloning and analysis of fetal ovary microRNAs in cattle. Anim Reprod Sci 2010, 120(1–4):16-22.
• [26]Li MZ, Liu YK, Wang T, Guan JQ, Luo ZG, Chen HS, Wang X, Chen L, Ma JD, Mu ZP, Jiang AA, Zhu L, Lang QL, Zhou XC, Wang JY, Zeng WX, Li N, Li K, Gao XL, Li XW: Repertoire of porcine microRNAs in adult ovary and testis by deep sequencing. Int J Biol Sci 2011, 7(7):1045-1055.
• [27]Mishima T, Takizawa T, Luo SS, Ishibashi O, Kawahigashi Y, Mizuguchi Y, Ishikawa T, Mori M, Kanda T, Goto T, Takizawa T: MicroRNA (miRNA) cloning analysis reveals sex differences in miRNA expression profiles between adult mouse testis and ovary. Reproduct 2008, 136(6):811-822.
• [28]Ahn HW, Morin RD, Zhao H, Harris RA, Coarfa C, Chen ZJ, Milosavljevic A, Marra MA, Rajkovic A: MicroRNA transcriptome in the newborn mouse ovaries determined by massive parallel sequencing. Mol Hum Reprod 2010, 16(7):463-471.
• [29]Carletti MZ, Fiedler SD, Christenson LK: MicroRNA 21 blocks apoptosis in mouse periovulatory granulosa cells. Biol Reprod 2010, 83(2):286-295.
• [30]Zhang JF, Ji XW, Zhou DD, Li YQ, Lin JK, Liu JL, Luo HS, Cui S: miR-143 is critical for the formation of primordial follicles in mice. Front Biosci-Landmark 2013, 18:588-597.
• [31]Yan GJ, Zhang LX, Fang T, Zhang Q, Wu SG, Jiang Y, Sun HX, Hu YL: MicroRNA-145 suppresses mouse granulosa cell proliferation by targeting activin receptor IB. Febs Lett 2012, 586(19):3263-3270.
• [32]Jovanovic VP, Sauer CM, Shawber CJ, Gomez R, Wang X, Sauer MV, Kitajewski J, Zimmermann RC: Intraovarian regulation of gonadotropin-dependent folliculogenesis depends on notch receptor signaling pathways not involving delta-like ligand 4 (Dll4). Reprod Biol Endocrin 2013, 11:43. BioMed Central Full Text
• [33]Trombly DJ, Woodruff TK, Mayo KE: Suppression of Notch signaling in the neonatal mouse ovary decreases primordial follicle formation. Endocrinol 2009, 150(2):1014-1024.
• [34]Vorontchikhina MA, Zimmermann RC, Shawber CJ, Tang HY, Kitajewski J: Unique patterns of Notch1, Notch4 and Jagged1 expression in ovarian vessels during folliculogenesis and corpus luteum formation. Gene Expr Patterns 2005, 5(5):701-709.
• [35]Craig J, Zhu H, Dyce PW, Petrik J, Li J: Leptin enhances oocyte nuclear and cytoplasmic maturation via the mitogen-activated protein kinase pathway. Endocrinol 2004, 145(11):5355-5363.
• [36]Ferrell JE Jr: Xenopus oocyte maturation: new lessons from a good egg. Bioessays 1999, 21(10):833-842.
• [37]Carlsbecker A, Lee JY, Roberts CJ, Dettmer J, Lehesranta S, Zhou J, Lindgren O, Moreno-Risueno MA, Vaten A, Thitamadee S, Campilho A, Sebastian J, Bowman JL, Helariutta Y, Benfey PN: Cell signalling by microRNA165/6 directs gene dose-dependent root cell fate. Nature 2010, 465(7296):316-321.
• [38]Tian T, Wang Y, Wang H, Zhu Z, Xiao Z: Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy. J Cell Biochem 2010, 111(2):488-496.
• [39]Kogure T, Lin WL, Yan IK, Braconi C, Patel T: Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology 2011, 54(4):1237-1248.
• [40]Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, Gonzalez S, Sanchez-Cabo F, Gonzalez MA, Bernad A, Sanchez-Madrid F: Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2011, 2:282.
• [41]Aucher A, Rudnicka D, Davis DM: MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation. J Immunol 2013, 191(12):6250-6260.
• [42]Karsch FJ, Dahl GE, Evans NP, Manning JM, Mayfield KP, Moenter SM, Foster DL: Seasonal changes in gonadotropin-releasing hormone secretion in the ewe: alteration in response to the negative feedback action of estradiol. Biol Reprod 1993, 49(6):1377-1383.
• [43]Barrell GK, Moenter SM, Caraty A, Karsch FJ: Seasonal changes of gonadotropin-releasing hormone secretion in the ewe. Biol Reprod 1992, 46(6):1130-1135.
• [44]Sai Lakshmi S, Agrawal S: piRNABank: a web resource on classified and clustered Piwi-interacting RNAs. Nucl Acid R 2008, 36(Database issue):D173-D177.
• [45]Houwing S, Kamminga LM, Berezikov E, Cronembold D, Girard A, van den Elst H, Filippov DV, Blaser H, Raz E, Moens CB, Plasterk RH, Hannon GJ, Draper BW, Ketting RF: A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in zebrafish. Cell 2007, 129(1):69-82.
• [46]Girard A, Sachidanandam R, Hannon GJ, Carmell MA: A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 2006, 442(7099):199-202.
• [47]Lim SL, Tsend-Ayush E, Kortschak RD, Jacob R, Ricciardelli C, Oehler MK, Grutzner F: Conservation and expression of PIWI-Interacting RNA pathway genes in male and female adult gonad of amniotes. Biol Reprod 2013, 89(6):136.
• [48]Minakhina S, Changela N, Steward R: Zfrp8/PDCD2 is required in ovarian stem cells and interacts with the piRNA pathway machinery. Development 2014, 141(2):259-268.
• [49]Yan Z, Hu HY, Jiang X, Maierhofer V, Neb E, He L, Hu YH, Hu H, Li N, Chen W, Khaitovich P: Widespread expression of piRNA-like molecules in somatic tissues. Nucl Acid R 2011, 39(15):6596-6607.
• [50]Liu G, Lei B, Li Y, Tong K, Ding Y, Luo L, Xia X, Jiang S, Deng C, Xiong Y, Li F: Discovery of potential piRNAs from next generation sequences of the sexually mature porcine testes. PLoS One 2012, 7(4):e34770.
• [51]Campbell BK, Gordon BM, Scaramuzzi RJ: The effect of ovarian arterial infusion of transforming growth factor alpha on ovarian follicle populations and ovarian hormone secretion in ewes with an autotransplanted ovary. J Endocrinol 1994, 143(1):13-24.
• [52]McNeilly JR, McNeilly AS, Walton JS, Cunningham FJ: Development and application of a heterologous radioimmunoassay for ovine follicle-stimulating hormone. J Endocrinol 1976, 70(1):69-79.
• [53]McNeilly AS, Jonassen JA, Fraser HM: Suppression of follicular development after chronic LHRH immunoneutralization in the ewe. J Reprod Fertil 1986, 76(1):481-490.
• [54]Djahanbakhch O, Swanton IA, Corrie JE, McNeilly AS: Prediction of ovulation by progesterone. Lancet 1981, 2(8256):1164-1165.
• [55]McNeilly AS: Changes in FSH and the pulsatile secretion of LH during the delay in oestrus induced by treatment of ewes with bovine follicular fluid. J Reprod Fertil 1984, 72(1):165-172.
• [56]Cumming IA, Brown JM, Goding JR, Bryant GD, Greenwood FC: Secretion of prolactin and luteinizing hormone at oestrus in the ewe. J Endocrinol 1972, 54(2):207-213.
• [57]Zhao WM, Liu WF, Tian DM, Tang BX, Wang YQ, Yu CX, Li RJ, Ling YC, Wu JY, Song SH, Hu SN: wapRNA: a web-based application for the processing of RNA sequences. Bioinformatics 2011, 27(21):3076-3077.
• [58]Friedlander MR, Mackowiak SD, Li N, Chen W, Rajewsky N: miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucl Acid R 2012, 40(1):37-52.
• [59]Robinson MD, McCarthy DJ, Smyth GK: edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26(1):139-140.
• [60]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-Delta Delta C) method. Methods 2001, 25(4):402-408.
• [61]Langmead B, Trapnell C, Pop M, Salzberg SL: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 2009, 10(3):R25. BioMed Central Full Text
• [62]Rosenkranz D, Zischler H: proTRAC - a software for probabilistic piRNA cluster detection, visualization and analysis. BMC Bioinformatics 2012, 13:5. BioMed Central Full Text