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Non-coding RNA in Ovarian Development and Disease

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Non-coding RNA and the Reproductive System

Abstract

The ovary’s primary function is to produce the mature female gamete, the oocyte that, following fertilization, can develop into an embryo, implant within the uterus and ultimately allow the mother’s genetic material to be passed along to subsequent generations. In addition to supporting the generation of the oocyte, the ovary and specific ephemeral tissues within it, follicles and corpora lutea, produce steroids that regulate all aspects of the reproductive system, including the hypothalamic/pituitary axis, the reproductive tract (uterus, oviduct, cervix), secondary sex characteristics all of which are also essential for pregnancy and subsequent nurturing of the offspring. To accomplish these critical roles, ovarian development and function are tightly regulated by a number of exogenous (hypothalamic/pituitary) and endogenous (intraovarian) hormones. Within ovarian cells, intricate signalling cascades and transcriptional and post-transcriptional gene regulatory networks respond to these hormonal influences to provide the exquisite control over all of the temporal and spatial events that must be synchronized to allow this organ to successfully complete its function. This book chapter will focus specifically on the role of non-coding RNAs, their identification and described functional roles within the ovary with respect to normal function and their possible involvement in diseases, which involve the ovary.

Grant support: Supported by a grant from the National Institutes of Health (HD061580; LKC).

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References

  • Ahn HW et al (2010) MicroRNA transcriptome in the newborn mouse ovaries determined by massive parallel sequencing. Mol Hum Reprod 16(7):463–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andl T et al (2006) The miRNA-processing enzyme dicer is essential for the morphogenesis and maintenance of hair follicles. Curr Biol 16(10):1041–1049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arango NA et al (2008) A mesenchymal perspective of müllerian duct differentiation and regression in Amhr2‐lacZ mice. Mol Reprod Dev 75(7):1154–1162

    Article  CAS  PubMed  Google Scholar 

  • Ariel I et al (1995) The imprinted H19 gene as a tumor marker in bladder carcinoma. Urology 45(2):335–338

    Article  CAS  PubMed  Google Scholar 

  • Bernstein E et al (2003) Dicer is essential for mouse development. Nat Genet 35(3):215–217

    Article  CAS  PubMed  Google Scholar 

  • Blower PE et al (2008) MicroRNAs modulate the chemosensitivity of tumor cells. Mol Cancer Ther 7(1):1–9

    Article  CAS  PubMed  Google Scholar 

  • Boren T et al (2009) MicroRNAs and their target messenger RNAs associated with ovarian cancer response to chemotherapy. Gynecol Oncol 113(2):249–255

    Article  CAS  PubMed  Google Scholar 

  • Boutzios G, Karalaki M, Zapanti E (2013) Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Impact on fertility. Endocrine 43(2):314–317

    Article  CAS  PubMed  Google Scholar 

  • Brewer CJ, Balen AH (2010) The adverse effects of obesity on conception and implantation. Reproduction 140(3):347–364

    Article  CAS  PubMed  Google Scholar 

  • Buccione R, Schroeder AC, Eppig JJ (1990) Interactions between somatic cells and germ cells throughout mammalian oogenesis. Biol Reprod 43(4):543–547

    Article  CAS  PubMed  Google Scholar 

  • Carletti M, Christenson LK (2009) MicroRNA in the ovary and female reproductive tract. J Anim Sci 87(14 suppl):E29–E38

    Article  CAS  PubMed  Google Scholar 

  • Carletti MZ, Fiedler SD, Christenson LK (2010) MicroRNA 21 blocks apoptosis in mouse periovulatory granulosa cells. Biol Reprod 83(2):286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carrer M et al (2012) Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc Natl Acad Sci U S A 109(38):15330–15335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castillo AF et al (2011) Hormone-dependent expression of a steroidogenic acute regulatory protein natural antisense transcript in MA-10 mouse tumor Leydig cells. PLoS One 6(8):e22822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y-H et al (2013) MiRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance. Diabetes 62:2278–2286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi Y et al (2007) Microarray analyses of newborn mouse ovaries lacking Nobox. Biol Reprod 77(2):312–319

    Article  CAS  PubMed  Google Scholar 

  • Cochrane DR et al (2010) Loss of miR-200c: a marker of aggressiveness and chemoresistance in female reproductive cancers. J Oncol 2009

    Google Scholar 

  • Cui X-S, Shen X-H, Kim N-H (2007) Dicer1 expression in preimplantation mouse embryos: involvement of Oct3/4 transcription at the blastocyst stage. Biochem Biophys Res Commun 352(1):231–236

    Google Scholar 

  • Di Leva G, Croce CM (2013) The role of microRNAs in the tumorigenesis of ovarian cancer. Front Oncol 3:153

    PubMed  PubMed Central  Google Scholar 

  • Ehrmann DA (2005) Polycystic ovary syndrome. N Engl J Med 352(12):1223–1236

    Article  CAS  PubMed  Google Scholar 

  • Eppig JJ (2001) Oocyte control of ovarian follicular development and function in mammals. Reproduction 122(6):829–838

    Article  CAS  PubMed  Google Scholar 

  • Fiedler SD et al. (2008) MicroRNA expression within periovulatory mural granulosa cells. Biology Reproduction 79:1030–1037

    Google Scholar 

  • Franks S (1995) Polycystic ovary syndrome. N Engl J Med 333(13):853–861

    Article  CAS  PubMed  Google Scholar 

  • Gifford JAH, Hunzicker-Dunn ME, Nilson JH (2009) Conditional deletion of beta-catenin mediated by Amhr2cre in mice causes female infertility. Biol Reprod 80(6):1282–1292

    Article  Google Scholar 

  • Gilchrist RB, Ritter LJ, Armstrong DT (2004) Oocyte–somatic cell interactions during follicle development in mammals. Anim Reprod Sci 82:431–446

    Article  PubMed  Google Scholar 

  • Gonzalez G, Behringer RR (2009) Dicer is required for female reproductive tract development and fertility in the mouse. Mol Reprod Dev 76(7):678–688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harfe BD et al (2005) The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102(31):10898–10903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong X et al (2008) Dicer1 is essential for female fertility and normal development of the female reproductive system. Endocrinology 149(12):6207–6212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hossain MM et al (2013) Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model. J Ovarian Res 6(1):36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussein-Fikret S, Fuller PJ (2005) Expression of nuclear receptor coregulators in ovarian stromal and epithelial tumours. Mol Cell Endocrinol 229(1–2):149–160

    Article  CAS  PubMed  Google Scholar 

  • Knuutila S et al (1998) DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Pathol 152(5):1107

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar MS et al (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39(5):673–677

    Article  CAS  PubMed  Google Scholar 

  • Kumarswamy R, Volkmann I, Thum T (2011) Regulation and function of miRNA-21 in health and disease. RNA Biol 8(5):706–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kung JT, Colognori D, Lee JT (2013) Long noncoding RNAs: past, present, and future. Genetics 193(3):651–669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lau NC et al (2009) Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line. Genome Res 19(10):1776–1785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lei L et al (2010) The regulatory role of Dicer in folliculogenesis in mice. Mol Cell Endocrinol 315(1):63–73

    Article  CAS  PubMed  Google Scholar 

  • Li SD et al (2010) The role of microRNAs in ovarian cancer initiation and progression. J Cell Mol Med 14(9):2240–2249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li M et al (2011) Repertoire of porcine microRNAs in adult ovary and testis by deep sequencing. Int J Biol Sci 7(7):1045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang Y et al (2007) Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 8(1):166

    Article  PubMed  PubMed Central  Google Scholar 

  • Liang M et al (2013) Transcriptional cooperation between p53 and NF-κB p65 regulates microRNA-224 transcription in mouse ovarian granulosa cells. Mol Cell Endocrinol 370:119–129

    Article  CAS  PubMed  Google Scholar 

  • Lin F et al (2012) miR-26b promotes granulosa cell apoptosis by targeting ATM during follicular atresia in porcine ovary. PLoS ONE 7(6):e38640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luense LJ et al (2011) Developmental programming: gestational testosterone treatment alters fetal ovarian gene expression. Endocrinology 152(12):4974–4983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma J et al (2010) MicroRNA activity is suppressed in mouse oocytes. Curr Biol 20(3):265–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma T et al (2011) Microarray analysis of differentially expressed microRNAs in non-regressed and regressed bovine corpus luteum tissue; microRNA-378 may suppress luteal cell apoptosis by targeting the interferon gamma receptor 1 gene. J Appl Genet 52(4):481–486

    Article  CAS  PubMed  Google Scholar 

  • Mase Y et al (2012) MiR-21 is enriched in the RNA-induced silencing complex and targets COL4A1 in human granulosa cell lines. Reprod Sci 19:1030–1040

    Article  PubMed  Google Scholar 

  • Mattiske DM, Han L, Mann JR (2009) Meiotic maturation failure induced by DICER1 deficiency is derived from primary oocyte ooplasm. Reproduction 137(4):625–632

    Article  CAS  PubMed  Google Scholar 

  • McBride D et al (2012) Identification of miRNAs associated with the follicular-luteal transition in the ruminant ovary. Reproduction 144(2):221–233

    Article  CAS  PubMed  Google Scholar 

  • Merritt WM et al (2008) Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med 359(25):2641–2650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muljo SA et al (2005) Aberrant T cell differentiation in the absence of Dicer. J Exp Med 202(2):261–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murchison EP et al (2007) Critical roles for Dicer in the female germline. Genes Dev 21(6):682–693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagaraja AK et al (2008) Deletion of Dicer in somatic cells of the female reproductive tract causes sterility. Mol Endocrinol 22(10):2336–2352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Otsuka M et al (2008) Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice. J Clin Invest 118(5):1944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pangas SA et al (2007) Intraovarian activins are required for female fertility. Mol Endocrinol 21(10):2458–2471

    Article  CAS  PubMed  Google Scholar 

  • Pastorelli LM et al (2009) Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract. Mamm Genome 20(3):140–151

    Article  PubMed  Google Scholar 

  • Richards JS (1980) Maturation of ovarian follicles: actions and interactions of pituitary and ovarian hormones on follicular cell differentiation. Physiol Rev 60(1):51–89

    CAS  PubMed  Google Scholar 

  • Richards JAS et al (2002a) Expression of FKHR, FKHRL1, and AFX genes in the rodent ovary: evidence for regulation by IGF-I, estrogen, and the gonadotropins. Mol Endocrinol 16(3):580

    Article  CAS  PubMed  Google Scholar 

  • Richards JS et al (2002b) Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization. Recent Prog Horm Res 57(1):195–220

    Article  CAS  PubMed  Google Scholar 

  • Ro S et al (2007) Cloning and expression profiling of small RNAs expressed in the mouse ovary. RNA 13(12):2366–2380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sang Q et al (2013) Identification of microRNAs in human follicular fluid: characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo. J Clin Endocrinol Metab 98(7):3068–3079

    Article  CAS  PubMed  Google Scholar 

  • Sirotkin AV et al (2009) Identification of MicroRNAs controlling human ovarian cell steroidogenesis via a genome‐scale screen. J Cell Physiol 219(2):415–420

    Article  CAS  PubMed  Google Scholar 

  • Sorrentino A et al (2008) Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol 111(3):478

    Article  CAS  PubMed  Google Scholar 

  • Suh N et al (2010) MicroRNA function is globally suppressed in mouse oocytes and early embryos. Curr Biol 20(3):271–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takada S et al (2006) Mouse microRNA profiles determined with a new and sensitive cloning method. Nucleic Acids Res 34(17):e115

    Article  PubMed  PubMed Central  Google Scholar 

  • Tang F et al (2007) Maternal microRNAs are essential for mouse zygotic development. Genes Dev 21(6):644–648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tilly JL et al (1991) Involvement of apoptosis in ovarian follicular atresia and postovulatory regression. Endocrinology 129(5):2799–2801

    Article  CAS  PubMed  Google Scholar 

  • Torley KJ et al (2011) Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation. Reprod Biol Endocrinol 9:2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tripurani SK et al (2010) Cloning and analysis of fetal ovary microRNAs in cattle. Anim Reprod Sci 120(1):16–22

    Article  CAS  PubMed  Google Scholar 

  • Veiga-Lopez A et al (2013) Developmental programming: gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression. Endocrinology 154(5):1873–1884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang W et al (2011) Interference RNA-based silencing of endogenous SMAD4 in porcine granulosa cells resulted in decreased FSH-mediated granulosa cells proliferation and steroidogenesis. Reproduction 141(5):643–651

    Article  CAS  PubMed  Google Scholar 

  • Watanabe 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(13):1732–1743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe T et al (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453(7194):539–543

    Article  CAS  PubMed  Google Scholar 

  • Xu S et al (2011) Micro-RNA378 (miR-378) regulates ovarian estradiol production by targeting aromatase. Endocrinology 152(10):3941–3951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan G et al (2012) MicroRNA-145 suppresses mouse granulosa cell proliferation by targeting activin receptor IB. FEBS Lett 586(19):3263–3270

    Article  CAS  PubMed  Google Scholar 

  • Yang N et al (2008) MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res 68(24):10307–10314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang CX et al (2012a) Small RNA profile of the cumulus-oocyte complex and early embryos in the pig. Biol Reprod 87(5):117

    Article  PubMed  Google Scholar 

  • Yang X et al (2012b) Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis. Reproduction 144(2):235–244

    Article  CAS  PubMed  Google Scholar 

  • Yao N et al (2009) A network of miRNAs expressed in the ovary are regulated by FSH. Front Biosci 14:3239–3245

    Article  CAS  Google Scholar 

  • Yao G et al (2010a) MicroRNA-224 is involved in transforming growth factor-β-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4. Mol Endocrinol 24(3):540–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao N et al (2010b) Follicle-stimulating hormone regulation of microRNA expression on progesterone production in cultured rat granulosa cells. Endocrine 38(2):158–166

    Article  CAS  PubMed  Google Scholar 

  • Yin M et al (2012a) Transactivation of microRNA-383 by steroidogenic factor-1 promotes estradiol release from mouse ovarian granulosa cells by targeting RBMS1. Mol Endocrinol 26(7):1129–1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin QF et al (2012b) Long noncoding RNAs with snoRNA ends. Mol Cell 48(2):219–230

    Article  CAS  PubMed  Google Scholar 

  • Zhang L et al (2006) MicroRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci 103(24):9136–9141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Q et al (2013) MicroRNA-181a suppresses mouse granulosa cell proliferation by targeting activin receptor IIA. PLoS ONE 8(3):e59667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao H, Rajkovic A (2008) MicroRNAs and mammalian ovarian development. In: Chegini N (ed) Seminars in reproductive medicine. © Thieme Medical Publishers, Stuttgart

    Google Scholar 

  • Zhou Y, Zhu Y, Zhang SH, Wang HM, Wang SY, Yang XK (2011) MicroRNA expression profiles in premature ovarian failure patients and its potential regulate functions. Chin J Birth Health Hered 19:20–22

    Google Scholar 

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Correspondence to Lane K. Christenson Ph.D. .

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Fitzgerald, J.B., George, J., Christenson, L.K. (2016). Non-coding RNA in Ovarian Development and Disease. In: Wilhelm, D., Bernard, P. (eds) Non-coding RNA and the Reproductive System. Advances in Experimental Medicine and Biology, vol 886. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7417-8_5

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