{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:57:03Z","timestamp":1769525823194,"version":"3.49.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:00:00Z","timestamp":1604966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:00:00Z","timestamp":1604966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31530087"],"award-info":[{"award-number":["31530087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFC0503200"],"award-info":[{"award-number":["2016YFC0503200"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007825","name":"State Forestry Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Genomics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hibernation in an appropriate environment not only is important for the survival of hibernators in winter, but also is crucial for breeding in the following season for many hibernating species. However, the genetic and epigenetic mechanism underlying this process remain unclear. In the current study, we performed an integrative multi-omics analysis of gonads collected from Chinese alligators that overwintered in wild cave and artificial warmroom to explore transcriptomic and epigenomic alternations in these organs.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The data revealed that in the breeding season, female alligators were more strongly affected in terms of gene expression than males by non-hibernation because of overwintering in a warm room, especially for genes related to oocyte maturation, and this effect commenced in winter with the downregulation of <jats:italic>STAR<\/jats:italic>, which is the rate limiting factor of steroid biosynthesis. Further, miRNAs were found to play essential roles in this negative effect of overwintering in the warm room on hibernation. The upregulated miRNAs likely were responsible for the suppression of oocyte maturation in the breeding season. Finally, DNA methylome changes, especially hypomethylation, were found to play an important role in the alterations in ovarian function-related gene expression induced by non-hibernation.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our study revealed the crucial role of hibernation quality for oocyte maturation in the Chinese alligator and the underlying genetic and epigenetic mechanisms, and highlights the importance of habitat, and especially, the overwintering site, in the conservation of not only the Chinese alligator, but also other endangered hibernators.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12864-020-07187-5","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:09:00Z","timestamp":1604966940000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multi-omics analysis reveals that natural hibernation is crucial for oocyte maturation in the female Chinese alligator"],"prefix":"10.1186","volume":"21","author":[{"given":"Jian-Qing","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu-Hong","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2051-2516","authenticated-orcid":false,"given":"Sheng-Guo","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,10]]},"reference":[{"key":"7187_CR1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/978-1-4614-1518-3_16","volume-title":"Wildlife behavior and conservation","author":"RH Yahner","year":"2012","unstructured":"Yahner RH. Winter Strategies. In: Wildlife behavior and conservation. New York: Springer; 2012. p. 139\u201343."},{"issue":"2","key":"7187_CR2","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1002\/cphy.c140064","volume":"6","author":"JF Staples","year":"2016","unstructured":"Staples JF. Metabolic flexibility: hibernation, torpor, and estivation. Compr Physiol. 2016;6(2):737\u201371.","journal-title":"Compr Physiol"},{"issue":"3","key":"7187_CR3","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1111\/mec.14483","volume":"27","author":"SL Faherty","year":"2018","unstructured":"Faherty SL, Villanueva-Canas JL, Blanco MB, Alba MM, Yoder AD. Transcriptomics in the wild: hibernation physiology in free-ranging dwarf lemurs. Mol Ecol. 2018;27(3):709\u201322.","journal-title":"Mol Ecol"},{"key":"7187_CR4","doi-asserted-by":"crossref","unstructured":"Lin JQ, Huang YY, Bian MY, Wan QH, Fang SG. A unique energy-saving strategy during hibernation revealed by multi-omics analysis in the Chinese alligator. iScience. 2020;23:101202.","DOI":"10.1016\/j.isci.2020.101202"},{"key":"7187_CR5","unstructured":"Barnes BM. Relationships between hibernation and reproduction in male ground squirrels. In: Adaptations to the cold: tenth international hibernation symposium. Armidale: University of New England Press; 1996. p. 71\u201380."},{"issue":"3","key":"7187_CR6","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1093\/jmammal\/gyw013","volume":"97","author":"GE Morrow","year":"2016","unstructured":"Morrow GE, Jones SM, Nicol SC. Interaction of hibernation and male reproductive function in wild Tasmanian echidnas Tachyglossus aculeatus setosus. J Mammal. 2016;97(3):852\u201360.","journal-title":"J Mammal"},{"issue":"5","key":"7187_CR7","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1086\/515857","volume":"70","author":"MT Mendonca","year":"1997","unstructured":"Mendonca MT, Hopkins WA. Effects of arousal from hibernation and plasma androgen levels on mating behavior in the male big brown bat, Eptesicus fuscus. Physiol Zool. 1997;70(5):556\u201362.","journal-title":"Physiol Zool"},{"issue":"4","key":"7187_CR8","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1080\/00063657.2017.1408566","volume":"64","author":"AE Goodenough","year":"2017","unstructured":"Goodenough AE, Coker DG, Wood MJ, Rogers SL. Overwintering habitat links to summer reproductive success: intercontinental carry-over effects in a declining migratory bird revealed using stable isotope analysis. Bird Stud. 2017;64(4):433\u201344.","journal-title":"Bird Stud"},{"key":"7187_CR9","volume-title":"Research on Chinese Alligator","author":"BH Chen","year":"2003","unstructured":"Chen BH, Hua TM, Wu XB, Wang CL. Research on Chinese Alligator. Shanghai: Shanghai Scientific and Technological Education Publishing House; 2003."},{"issue":"1","key":"7187_CR10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3354\/esr00648","volume":"27","author":"FE Santana","year":"2015","unstructured":"Santana FE, Swaisgood RR, Lemm JM, Fisher RN, Clark RW. Chilled frogs are hot: hibernation and reproduction of the endangered mountain yellow-legged frog Rana muscosa. Endanger Species Res. 2015;27(1):43\u201351.","journal-title":"Endanger Species Res"},{"issue":"4","key":"7187_CR11","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1007\/BF00380044","volume":"74","author":"TI Olsson","year":"1988","unstructured":"Olsson TI. The effect of wintering sites on the survival and reproduction of Gyraulus-Acronicus (Gastropoda) in a partly frozen river. Oecologia. 1988;74(4):492\u20135.","journal-title":"Oecologia"},{"issue":"4","key":"7187_CR12","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.theriogenology.2009.09.033","volume":"73","author":"TL Roth","year":"2010","unstructured":"Roth TL, Szymanski DC, Keyster ED. Effects of age, weight, hormones, and hibernation on breeding success in boreal toads (Bufo boreas boreas). Theriogenology. 2010;73(4):501\u201311.","journal-title":"Theriogenology"},{"issue":"4","key":"7187_CR13","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1071\/RD18073_CO","volume":"31","author":"S Poo","year":"2019","unstructured":"Poo S, Hinkson KM, Stege E, Terrell KA. Sperm output and body condition are maintained independently of hibernation in an endangered temperate amphibian. Reprod Fert Develop. 2019;31(4):827.","journal-title":"Reprod Fert Develop"},{"issue":"3","key":"7187_CR14","first-page":"284","volume":"36","author":"LM Fang","year":"2015","unstructured":"Fang LM, Zhai T, Zhao L, Fang SG. Deep brumation features of Zhejiang Chinese alligators. Chin J Wildl. 2015;36(3):284\u20137.","journal-title":"Chin J Wildl"},{"issue":"2","key":"7187_CR15","first-page":"298","volume":"25","author":"TS Xia","year":"2006","unstructured":"Xia TS, Zhou KH, Zhu JL. Influence of Hibernant temperature on reproduction of Chinese alligator. Sichuan J Zool. 2006;25(2):298\u2013399.","journal-title":"Sichuan J Zool"},{"issue":"2","key":"7187_CR16","first-page":"400","volume":"25","author":"TS Xia","year":"2006","unstructured":"Xia TS, L. ZJ, M S: relationship between temperature and diseases occurrence of Chinese alligator during hibernation. Sichuan J Zool. 2006;25(2):400\u20132.","journal-title":"Sichuan J Zool"},{"issue":"2","key":"7187_CR17","first-page":"57","volume":"7","author":"GL Zhang","year":"2003","unstructured":"Zhang GL, Geng YJ, XIao JG, Yang SH. Comparison of two overwintering ways for Chinese alligator in captivity. J Econ Anim. 2003;7(2):57\u20139.","journal-title":"J Econ Anim"},{"key":"7187_CR18","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.cbpb.2016.05.001","volume":"200","author":"R Zhang","year":"2016","unstructured":"Zhang R, Hu Y, Wang H, Yan P, Zhou Y, Wu R, Wu X. Molecular cloning, characterization, tissue distribution and mRNA expression changes during the hibernation and reproductive periods of estrogen receptor alpha (ESR1) in Chinese alligator, Alligator sinensis. Comp Biochem Physiol B Biochem Mol Biol. 2016;200:28\u201335.","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"7187_CR19","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.cbpb.2015.01.003","volume":"183","author":"R Zhang","year":"2015","unstructured":"Zhang R, Zhang SZ, Zhu X, Zhou YK, Wu XB. Molecular characterization of the Chinese alligator follicle-stimulating hormone beta subunit (FSH beta) and its expression during the female reproductive cycle. Comp Biochem Phys B. 2015;183:49\u201357.","journal-title":"Comp Biochem Phys B"},{"key":"7187_CR20","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.anireprosci.2015.02.008","volume":"156","author":"R Zhang","year":"2015","unstructured":"Zhang R, Zhang S, Zhu X, Zhou Y, Wu X. Follicle-stimulating hormone receptor (FSHR) in Chinese alligator, Alligator sinensis: molecular characterization, tissue distribution and mRNA expression changes during the female reproductive cycle. Anim Reprod Sci. 2015;156:40\u201350.","journal-title":"Anim Reprod Sci"},{"key":"7187_CR21","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1071\/RD19332","volume":"32","author":"R Zhang","year":"2020","unstructured":"Zhang R, Nie H, Duan S, Yan P, Izaz A, Wang R, Zhou Y, Wu X. Cloning, characterization and expression profile of kisspeptin1 and the kisspeptin1 receptor at the hypothalamic-pituitary-ovarian axis (HPO) of Chinese alligator, Alligator sinensis, during the reproductive cycle. Reprod Fertil Dev. 2020;32:792\u2013804.","journal-title":"Reprod Fertil Dev"},{"issue":"2","key":"7187_CR22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1071\/ZO18005","volume":"66","author":"HJ Sun","year":"2018","unstructured":"Sun HJ, Zuo XB, Sun L, Yan P, Zhang F, Xue H, Li E, Zhou YK, Wu R, Wu XB. Insights into the seasonal adaptive mechanisms of Chinese alligators (Alligator sinensis) from transcriptomic analyses. Aust J Zool. 2018;66(2):93\u2013102.","journal-title":"Aust J Zool"},{"issue":"7","key":"7187_CR23","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1152\/physiolgenomics.00120.2015","volume":"48","author":"ST Cooper","year":"2016","unstructured":"Cooper ST, Sell SS, Fahrenkrog M, Wilkinson K, Howard DR, Bergen H, Cruz E, Cash SE, Andrews MT, Hampton M. Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels. Physiol Genomics. 2016;48(7):513\u201325.","journal-title":"Physiol Genomics"},{"issue":"8","key":"7187_CR24","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1093\/gbe\/evw163","volume":"8","author":"SL Faherty","year":"2016","unstructured":"Faherty SL, Villanueva-Canas JL, Klopfer PH, Alba MM, Yoder AD. Gene expression profiling in the hibernating primate, Cheirogaleus medius. Genome Biol Evol. 2016;8(8):2413\u201326.","journal-title":"Genome Biol Evol"},{"issue":"12","key":"7187_CR25","doi-asserted-by":"publisher","first-page":"e85157","DOI":"10.1371\/journal.pone.0085157","volume":"8","author":"M Hampton","year":"2013","unstructured":"Hampton M, Melvin RG, Andrews MT. Transcriptomic analysis of brown adipose tissue across the physiological extremes of natural hibernation. PLoS One. 2013;8(12):e85157.","journal-title":"PLoS One"},{"issue":"9","key":"7187_CR26","doi-asserted-by":"publisher","first-page":"e107746","DOI":"10.1371\/journal.pone.0107746","volume":"9","author":"M Lei","year":"2014","unstructured":"Lei M, Dong D, Mu S, Pan YH, Zhang S. Comparison of brain transcriptome of the greater horseshoe bats (Rhinolophus ferrumequinum) in active and torpid episodes. PLoS One. 2014;9(9):e107746.","journal-title":"PLoS One"},{"issue":"2","key":"7187_CR27","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1002\/jcp.26030","volume":"233","author":"Y Luan","year":"2018","unstructured":"Luan Y, Ou J, Kunze VP, Qiao F, Wang Y, Wei L, Li W, Xie Z. Integrated transcriptomic and metabolomic analysis reveals adaptive changes of hibernating retinas. J Cell Physiol. 2018;233(2):1434\u201345.","journal-title":"J Cell Physiol"},{"issue":"22","key":"7187_CR28","doi-asserted-by":"publisher","first-page":"4489","DOI":"10.1111\/mec.14876","volume":"27","author":"RF Nespolo","year":"2018","unstructured":"Nespolo RF, Gaitan-Espitia JD, Quintero-Galvis JF, Fernandez FV, Silva AX, Molina C, Storey KB, Bozinovic F. A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation. Mol Ecol. 2018;27(22):4489\u2013500.","journal-title":"Mol Ecol"},{"issue":"9","key":"7187_CR29","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1038\/cr.2013.104","volume":"23","author":"QH Wan","year":"2013","unstructured":"Wan QH, Pan SK, Hu L, Zhu Y, Xu PW, Xia JQ, Chen H, He GY, He J, Ni XW, et al. Genome analysis and signature discovery for diving and sensory properties of the endangered Chinese alligator. Cell Res. 2013;23(9):1091\u2013105.","journal-title":"Cell Res."},{"key":"7187_CR30","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.anireprosci.2004.04.001","volume":"82-83","author":"GH Davis","year":"2004","unstructured":"Davis GH. Fecundity genes in sheep. Anim Reprod Sci. 2004;82-83:247\u201353.","journal-title":"Anim Reprod Sci"},{"issue":"1","key":"7187_CR31","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s003350010015","volume":"11","author":"MF Rothschild","year":"2000","unstructured":"Rothschild MF, Messer L, Day A, Wales R, Short T, Southwood O, Plastow G. Investigation of the retinol-binding protein 4 (RBP4) gene as a candidate gene for increased litter size in pigs. Mamm Genome. 2000;11(1):75\u20137.","journal-title":"Mamm Genome"},{"issue":"2","key":"7187_CR32","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.ydbio.2007.03.007","volume":"305","author":"BW Draper","year":"2007","unstructured":"Draper BW, McCallum CM. Moens CB: nanos1 is required to maintain oocyte production in adult zebrafish. Dev Biol. 2007;305(2):589\u201398.","journal-title":"Dev Biol"},{"issue":"10","key":"7187_CR33","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1172\/JCI8635","volume":"105","author":"T Shindo","year":"2000","unstructured":"Shindo T, Kurihara H, Kuno K, Yokoyama H, Wada T, Kurihara Y, Imai T, Wang Y, Ogata M, Nishimatsu H, et al. ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function. J Clin Invest. 2000;105(10):1345\u201352.","journal-title":"J Clin Invest"},{"issue":"3","key":"7187_CR34","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1210\/edrv.19.3.0334","volume":"19","author":"C Bole-Feysot","year":"1998","unstructured":"Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998;19(3):225\u201368.","journal-title":"Endocr Rev"},{"issue":"1","key":"7187_CR35","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1210\/en.2010-0636","volume":"152","author":"K Kashimada","year":"2011","unstructured":"Kashimada K, Pelosi E, Chen H, Schlessinger D, Wilhelm D, Koopman P. FOXL2 and BMP2 act cooperatively to regulate follistatin gene expression during ovarian development. Endocrinology. 2011;152(1):272\u201380.","journal-title":"Endocrinology"},{"issue":"4","key":"7187_CR36","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.scib.2018.01.004","volume":"63","author":"JQ Lin","year":"2018","unstructured":"Lin JQ, Zhou Q, Yang HQ, Fang LM, Tang KY, Sun L, Wan QH, Fang SG. Molecular mechanism of temperature-dependent sex determination and differentiation in Chinese alligator revealed by developmental transcriptome profiling. Sci Bull. 2018;63(4):209\u201312.","journal-title":"Sci Bull"},{"issue":"3","key":"7187_CR37","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.semcdb.2008.10.010","volume":"20","author":"CM Shoemaker","year":"2009","unstructured":"Shoemaker CM, Crews D. Analyzing the coordinated gene network underlying temperature-dependent sex determination in reptiles. Semin Cell Dev Biol. 2009;20(3):293\u2013303.","journal-title":"Semin Cell Dev Biol"},{"issue":"4","key":"7187_CR38","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/j.1463-6395.1984.tb01045.x","volume":"65","author":"CB Jorgensen","year":"1984","unstructured":"Jorgensen CB. Relations between hibernation and ovarian functions in a temperate zone frog, Rana-Temporaria. Acta Zool. 1984;65(4):239\u201347.","journal-title":"Acta Zool"},{"issue":"10","key":"7187_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078785","volume":"8","author":"Z Kuang","year":"2013","unstructured":"Kuang Z, Yao Y, Shi Y, Gu Z, Sun Z, Tso J. Winter hibernation and UCHL1-p34cdc2 association in toad oocyte maturation competence. PLoS One. 2013;8(10):e78785.","journal-title":"PLoS One"},{"issue":"3","key":"7187_CR40","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1007\/s00441-012-1469-6","volume":"349","author":"MM Hossain","year":"2012","unstructured":"Hossain MM, Sohel MM, Schellander K, Tesfaye D. Characterization and importance of microRNAs in mammalian gonadal functions. Cell Tissue Res. 2012;349(3):679\u201390.","journal-title":"Cell Tissue Res"},{"issue":"6","key":"7187_CR41","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.tem.2009.05.001","volume":"20","author":"LJ Luense","year":"2009","unstructured":"Luense LJ, Carletti MZ, Christenson LK. Role of dicer in female fertility. Trends Endocrinol Metab. 2009;20(6):265\u201372.","journal-title":"Trends Endocrinol Metab"},{"issue":"9\u201310","key":"7187_CR42","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1007\/s10815-010-9456-x","volume":"27","author":"H-C Liu","year":"2010","unstructured":"Liu H-C, Tang Y, He Z, Rosenwaks Z. Dicer is a key player in oocyte maturation. J Assist Reprod Genet. 2010;27(9\u201310):571\u201380.","journal-title":"J Assist Reprod Genet"},{"issue":"3","key":"7187_CR43","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cub.2009.12.044","volume":"20","author":"N Suh","year":"2010","unstructured":"Suh N, Baehner L, Moltzahn F, Melton C, Shenoy A, Chen J, Blelloch R. MicroRNA function is globally suppressed in mouse oocytes and early embryos. Curr Biol. 2010;20(3):271\u20137.","journal-title":"Curr Biol"},{"issue":"2","key":"7187_CR44","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1002\/jcp.21689","volume":"219","author":"AV Sirotkin","year":"2009","unstructured":"Sirotkin AV, Ovcharenko D, Grossmann R, Laukova M, Mlyncek M. Identification of microRNAs controlling human ovarian cell steroidogenesis via a genome-scale screen. J Cell Physiol. 2009;219(2):415\u201320.","journal-title":"J Cell Physiol"},{"issue":"5871","key":"7187_CR45","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1126\/science.1153069","volume":"319","author":"R Kucharski","year":"2008","unstructured":"Kucharski R, Maleszka J, Foret S, Maleszka R. Nutritional control of reproductive status in honeybees via DNA methylation. Science. 2008;319(5871):1827\u201330.","journal-title":"Science"},{"issue":"1780","key":"7187_CR46","doi-asserted-by":"publisher","first-page":"20132502","DOI":"10.1098\/rspb.2013.2502","volume":"281","author":"HE Amarasinghe","year":"2014","unstructured":"Amarasinghe HE, Clayton CI, Mallon EB. Methylation and worker reproduction in the bumble-bee (Bombus terrestris). Proc R Soc B-Biol Sci. 2014;281(1780):20132502.","journal-title":"Proc R Soc B-Biol Sci"},{"issue":"2","key":"7187_CR47","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.gene.2015.09.006","volume":"575","author":"Y Si","year":"2016","unstructured":"Si Y, Ding Y, He F, Wen H, Li J, Zhao J, Huang Z. DNA methylation level of cyp19a1a and Foxl2 gene related to their expression patterns and reproduction traits during ovary development stages of Japanese flounder (Paralichthys olivaceus). Gene. 2016;575(2):321\u201330.","journal-title":"Gene"},{"issue":"1","key":"7187_CR48","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.gene.2013.05.037","volume":"527","author":"Y Ding","year":"2013","unstructured":"Ding Y, He F, Wen H, Li J, Ni M, Chi M, Qian K, Bu Y, Zhang D, Si Y. DNA methylation status of cyp17-II gene correlated with its expression pattern and reproductive endocrinology during ovarian development stages of Japanese flounder (Paralichthys olivaceus). Gene. 2013;527(1):82\u20138.","journal-title":"Gene"},{"issue":"3","key":"7187_CR49","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1007\/s10695-015-0187-x","volume":"42","author":"J Bai","year":"2016","unstructured":"Bai J, Gong W, Wang C, Gao Y, Hong W, Chen SX. Dynamic methylation pattern of cyp19a1a core promoter during zebrafish ovarian folliculogenesis. Fish Physiol Biochem. 2016;42(3):947\u201354.","journal-title":"Fish Physiol Biochem"},{"issue":"1","key":"7187_CR50","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1186\/s12864-017-4068-9","volume":"18","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Li F, Feng X, Yang H, Zhu A, Pang J, Han L, Zhang T, Yao X, Wang F. Genome-wide analysis of DNA methylation profiles on sheep ovaries associated with prolificacy using whole-genome bisulfite sequencing. BMC Genomics. 2017;18(1):759.","journal-title":"BMC Genomics"},{"issue":"11","key":"7187_CR51","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.2174\/13816128113199990517","volume":"20","author":"R Calicchio","year":"2014","unstructured":"Calicchio R, Doridot L, Miralles F, Mehats C, Vaiman D. DNA methylation, an epigenetic mode of gene expression regulation in reproductive science. Curr Pharm Des. 2014;20(11):1726\u201350.","journal-title":"Curr Pharm Des"},{"issue":"4","key":"7187_CR52","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead B, Salzberg SL. Fast gapped-read alignment with bowtie 2. Nat Methods. 2012;9(4):357\u20139.","journal-title":"Nat Methods"},{"issue":"4","key":"7187_CR53","doi-asserted-by":"publisher","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","volume":"14","author":"D Kim","year":"2013","unstructured":"Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14(4):R36.","journal-title":"Genome Biol"},{"issue":"2","key":"7187_CR54","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders S, Pyl PT, Huber W. HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31(2):166\u20139.","journal-title":"Bioinformatics"},{"key":"7187_CR55","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1093\/bioinformatics\/btp612","volume":"26","author":"L Wang","year":"2010","unstructured":"Wang L, Feng Z, Wang X, Wang X, Zhang X. DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics. 2010;26:136\u20138.","journal-title":"Bioinformatics"},{"issue":"8","key":"7187_CR56","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.molp.2020.06.009","volume":"13","author":"C Chen","year":"2020","unstructured":"Chen C, Chen H, Zhang Y, Thomas HR, Frank MH, He Y, Xia R. TBtools: an integrative toolkit developed for interactive analyses of big biological data. Mol Plant. 2020;13(8):1194\u2013202.","journal-title":"Mol Plant"},{"issue":"10","key":"7187_CR57","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","volume":"11","author":"S Anders","year":"2010","unstructured":"Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol. 2010;11(10):R106.","journal-title":"Genome Biol"},{"issue":"D1","key":"7187_CR58","doi-asserted-by":"publisher","first-page":"D335","DOI":"10.1093\/nar\/gkx1038","volume":"46","author":"I Kalvari","year":"2018","unstructured":"Kalvari I, Argasinska J, Quinones-Olvera N, Nawrocki EP, Rivas E, Eddy SR, Bateman A, Finn RD, Petrov AI. Rfam 13.0: shifting to a genome-centric resource for non-coding RNA families. Nucleic Acids Res. 2018;46(D1):D335\u201342.","journal-title":"Nucleic Acids Res"},{"key":"7187_CR59","unstructured":"Smit AFA, Hubley R, Green P. RepeatMasker Open-4.0. 2013-2015. http:\/\/www.repeatmasker.org."},{"key":"7187_CR60","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/1471-2105-13-140","volume":"13","author":"M Wen","year":"2012","unstructured":"Wen M, Shen Y, Shi S. Tang T: miREvo: an integrative microRNA evolutionary analysis platform for next-generation sequencing experiments. BMC Bioinformatics. 2012;13:140.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"7187_CR61","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1093\/nar\/gkr688","volume":"40","author":"MR Friedlander","year":"2012","unstructured":"Friedlander MR, Mackowiak SD, Li N, Chen W. Rajewsky N: miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Res. 2012;40(1):37\u201352.","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"7187_CR62","doi-asserted-by":"publisher","first-page":"R90","DOI":"10.1186\/gb-2010-11-8-r90","volume":"11","author":"D Betel","year":"2010","unstructured":"Betel D, Koppal A, Agius P, Sander C, Leslie C. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol. 2010;11(8):R90.","journal-title":"Genome Biol"},{"issue":"10","key":"7187_CR63","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1038\/ng2135","volume":"39","author":"M Kertesz","year":"2007","unstructured":"Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E. The role of site accessibility in microRNA target recognition. Nat Genet. 2007;39(10):1278\u201384.","journal-title":"Nat Genet"},{"issue":"10","key":"7187_CR64","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1261\/rna.5248604","volume":"10","author":"M Rehmsmeier","year":"2004","unstructured":"Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effective prediction of microRNA\/target duplexes. RNA. 2004;10(10):1507\u201317.","journal-title":"RNA"},{"issue":"11","key":"7187_CR65","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","volume":"27","author":"F Krueger","year":"2011","unstructured":"Krueger F, Andrews SR. Bismark: a flexible aligner and methylation caller for bisulfite-Seq applications. Bioinformatics. 2011;27(11):1571\u20132.","journal-title":"Bioinformatics"},{"issue":"7","key":"7187_CR66","doi-asserted-by":"publisher","first-page":"e0132866","DOI":"10.1371\/journal.pone.0132866","volume":"10","author":"Z Wang","year":"2015","unstructured":"Wang Z, Li X, Jiang Y, Shao Q, Liu Q, Chen B. Huang D: swDMR: a sliding window approach to identify differentially methylated regions based on whole genome bisulfite sequencing. PLoS One. 2015;10(7):e0132866.","journal-title":"PLoS One"},{"issue":"2","key":"7187_CR67","doi-asserted-by":"publisher","first-page":"R14","DOI":"10.1186\/gb-2010-11-2-r14","volume":"11","author":"MD Young","year":"2010","unstructured":"Young MD, Wakefield MJ, Smyth GK, Oshlack A. Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol. 2010;11(2):R14.","journal-title":"Genome Biol"},{"issue":"19","key":"7187_CR68","doi-asserted-by":"publisher","first-page":"3787","DOI":"10.1093\/bioinformatics\/bti430","volume":"21","author":"X Mao","year":"2005","unstructured":"Mao X, Cai T, Olyarchuk JG, Wei L. Automated genome annotation and pathway identification using the KEGG Orthology (KO) as a controlled vocabulary. Bioinformatics. 2005;21(19):3787\u201393.","journal-title":"Bioinformatics"}],"container-title":["BMC Genomics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12864-020-07187-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12864-020-07187-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12864-020-07187-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:11:09Z","timestamp":1604967069000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgenomics.biomedcentral.com\/articles\/10.1186\/s12864-020-07187-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,10]]},"references-count":68,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["7187"],"URL":"https:\/\/doi.org\/10.1186\/s12864-020-07187-5","relation":{},"ISSN":["1471-2164"],"issn-type":[{"value":"1471-2164","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,10]]},"assertion":[{"value":"21 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All the experimental procedures with Chinese alligator in this study had been given prior approval by the Animal Ethics Committee of Zhejiang University (ZJU2015\u2013154-13) and the State Forestry Administration of China [Forest Conservation Permission Document (2014) 1545].","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"774"}}