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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2011

Open Access 01-12-2011 | Research

Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation

Authors: Katie J Torley, Juliano C da Silveira, Peter Smith, Russell V Anthony, DN Rao Veeramachaneni, Quinton A Winger, Gerrit J Bouma

Published in: Reproductive Biology and Endocrinology | Issue 1/2011

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Abstract

Background

Gonadal differentiation in the mammalian fetus involves a complex dose-dependent genetic network. Initiation and progression of fetal ovarian and testicular pathways are accompanied by dynamic expression patterns of thousands of genes. We postulate these expression patterns are regulated by small non-coding RNAs called microRNAs (miRNAs). The aim of this study was to identify the expression of miRNAs in mammalian fetal gonads using sheep as a model.

Methods

We determined the expression of 128 miRNAs by real time PCR in early-gestational (gestational day (GD) 42) and mid-gestational (GD75) sheep ovaries and testes. Expression data were further examined and validated by bioinformatic analysis.

Results

Expression analysis revealed significant differences between ovaries and testes among 24 miRNAs at GD42, and 43 miRNAs at GD75. Bioinformatic analysis revealed that a number of differentially expressed miRNAs are predicted to target genes known to be important in mammalian gonadal development, including ESR1, CYP19A1, and SOX9. In situ hybridization revealed miR-22 localization within fetal testicular cords. As estrogen signaling is important in human and sheep ovarian development, these data indicate that miR-22 is involved in repressing estrogen signaling within fetal testes.

Conclusions

Based on our results we postulate that gene expression networks underlying fetal gonadal development are regulated by miRNAs.
Appendix
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Literature
1.
Maatouk DM, Capel B: Sexual development of the soma in the mouse. Curr Top Dev Biol. 2008, 83: 151-183. full_text.CrossRefPubMed
2.
Sekido R, Lovell-Badge R: Sex determination and SRY: down to a wink and a nudge?. Trends Genet. 2009, 25: 19-29. 10.1016/j.tig.2008.10.008.CrossRefPubMed
3.
Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M: Genetic evidence equating SRY and the testis-determining factor. Nature. 1990, 348: 448-450. 10.1038/348448A0.CrossRefPubMed
4.
Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Munsterberg A, Vivian N, Goodfellow P, Lovell-Badge R: A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990, 346: 245-250. 10.1038/346245a0.CrossRefPubMed
5.
Chassot AA, Ranc F, Gregoire EP, Roepers-Gajadien HL, Taketo MM, Camerino G, de Rooij DG, Schedl A, Chaboissier MC: Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet. 2008, 17: 1264-1277. 10.1093/hmg/ddn016.CrossRefPubMed
6.
Tomizuka K, Horikoshi K, Kitada R, Sugawara Y, Iba Y, Kojima A, Yoshitome A, Yamawaki K, Amagai M, Inoue A, Oshima T, Kakitani M: R-spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling. Hum Mol Genet. 2008, 17: 1278-1291. 10.1093/hmg/ddn036.CrossRefPubMed
7.
Brennan J, Capel B: One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet. 2004, 5: 509-521. 10.1038/nrg1381.CrossRefPubMed
8.
Wilhelm D, Palmer S, Koopman P: Sex determination and gonadal development in mammals. Physiol Rev. 2007, 1: 1-28. 10.1152/physrev.00009.2006.CrossRef
9.
Yao HH, Matzuk MM, Jorgez CJ, Menke DB, Page DC, Swain A, Capel B: Follistatin operates downstream of Wnt4 in mammalian organogenesis. Dev Dyn. 2004, 230: 210-215. 10.1002/dvdy.20042.PubMedCentralCrossRefPubMed
10.
Small CL, Shima JE, Uzumcu M, Skinner MK, Griswold MD: Profiling gene expression during the differentiation and development of the murine embryonic gonad. Biol Reprod. 2005, 72: 492-501. 10.1095/biolreprod.104.033696.PubMedCentralCrossRefPubMed
11.
Nef S, Schaad O, Stallings NR, Cederroth CR, Pitetti JL, Schaer G, Malki S, Dubois-Dauphin M, Boizet-Bonhoure B, Descombes P, Parker KL, Vassalli JD: Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development. Dev Biol. 2005, 287: 361-377. 10.1016/j.ydbio.2005.09.008.CrossRefPubMed
12.
Beverdam A, Koopman P: Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes. Hum Mol Genet. 2006, 15: 417-431. 10.1093/hmg/ddi463.CrossRefPubMed
13.
Bouma GJ, Affourtit JP, Bult CJ, Eicher EM: Transcriptional profile of mouse pre-granulosa and Sertoli cells isolated from early-differentiated fetal gonads. Gene Expr Patterns. 2007, 7: 113-123. 10.1016/j.modgep.2006.05.011.CrossRefPubMed
14.
Bouma GJ, Hudson QJ, Washburn LL, Eicher EM: New candidate genes identified for controlling mouse gonadal sex determination and the early stages of granulosa and Sertoli cell differentiation. Biol Reprod. 2010, 82: 380-389. 10.1095/biolreprod.109.079822.PubMedCentralCrossRefPubMed
15.
Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5.CrossRefPubMed
16.
Fazi F, Nervi C: MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination. Cardiovasc Res. 2008, 79: 553-561. 10.1093/cvr/cvn151.CrossRefPubMed
17.
Fabian MR, Sonenberg N, Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Ann Rev Biochem. 2010, 79: 351-379. 10.1146/annurev-biochem-060308-103103.CrossRefPubMed
18.
Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T: Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002, 12: 735-739. 10.1016/S0960-9822(02)00809-6.CrossRefPubMed
19.
Hayashi K, Chuva de Sousa Lopes SM, Kaneda M, Tang F, Hajkova P, Lao K, O'Carroll D, Das PP, Tarakhovsky A, Miska EA, Surani MA: MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS One. 2008, 3: e1738-10.1371/journal.pone.0001738.PubMedCentralCrossRefPubMed
20.
Maatouk DM, Loveland KL, McManus MT, Moore K, Harfe BD: Dicer1 is required for differentiation of the mouse male germline. Biol Reprod. 2008, 79: 696-703. 10.1095/biolreprod.108.067827.CrossRefPubMed
21.
Papaioannou MD, Pitetti JL, Ro S, Park C, Aubry F, Schaad O, Vejnar CE, Kühne F, Descombes P, Zdobnov EM, McManus MT, Guillou F, Harfe BD, Yan W, Jegou B, Nef S: Sertoli cell Dicer is essential for spermatogenesis in mice. Dev Biol. 2009, 326: 250-259. 10.1016/j.ydbio.2008.11.011.PubMedCentralCrossRefPubMed
22.
Nagaraja AK, Andreu-Vieyra C, Franco HL, Ma L, Chen R, Han DY, Zhu H, Agno JE, Gunaratne PH, DeMayo FJ, Matzuk MM: Deletion of Dicer in somatic cells of the female reproductive tract causes sterility. Mol Endocrinol. 2008, 22: 2336-2352. 10.1210/me.2008-0142.PubMedCentralCrossRefPubMed
23.
Hong X, Luense LJ, McGinnis LK, Nothnick WB, Christenson LK: Dicer1 is essential for female fertility and normal development of the female reproductive system. Endocrinology. 2008, 149: 6207-6212. 10.1210/en.2008-0294.PubMedCentralCrossRefPubMed
24.
Gonzalez G, Behringer RR: Dicer is required for female reproductive tract development and fertility in the mouse. Mol Reprod Dev. 2009, 76: 678-688. 10.1002/mrd.21010.PubMedCentralCrossRefPubMed
25.
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. Reproduction. 2008, 136: 811-822. 10.1530/REP-08-0349.CrossRefPubMed
26.
Tripurani SK, Xiao C, Salem M, Yao J: Cloning and analysis of fetal ovary microRNAs in cattle. Anim Reprod Sci. 2010, 120: 16-22. 10.1016/j.anireprosci.2010.03.001.CrossRefPubMed
27.
Juengel JL, Sawyer HR, Smith PR, Quirke LD, Heath DA, Lun S, Wakefield St J, McNatty KP: Origins of follicular cells and ontogeny of steroidogenesis in ovine fetal ovaries. Mol Cell Endocrinol. 2002, 191: 1-10. 10.1016/S0303-7207(02)00045-X.CrossRefPubMed
28.
Sawyer HR, Smith P, Heath DA, Juengel JL, Wakefield St J, McNatty KP: Formation of ovarian follicles during fetal development in sheep. Biol Reprod. 2002, 66: 1134-1150. 10.1095/biolreprod66.4.1134.CrossRefPubMed
29.
30.
Akilesh S, Shaffer DJ, Roopenian D: Customized molecular phenotyping by quantitative gene expression and pattern recognition analysis. Genome Res. 2003, 13: 1719-1727. 10.1101/gr.533003.PubMedCentralCrossRefPubMed
31.
Bouma GJ, Hart GT, Washburn LL, Recknagel AK, Eicher EM: Using real time RT-PCR analysis to determine multiple gene expression patterns during XX and XY mouse fetal gonad development. Gene Expr Patterns. 2004, 5: 141-149. 10.1016/j.modgep.2004.05.001.CrossRefPubMed
32.
33.
Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Prot. 2008, 3: 1101-1108. 10.1038/nprot.2008.73.CrossRef
34.
35.
36.
37.
Payen E, Pailhoux E, Merhi RA, Gianquinto L, Kirszenbaum M, Locatelli A, Cotinot C: Characterization of ovine SRY transcript and developmental expression of genes involved in sexual differentiation. Int J Dev Biol. 1996, 40: 567-575.PubMed
38.
Quirke LD, Juenge JL, Tisda DJ, Lun S, Heath DA, McNatty KP: Ontogeny of steroidogenesis in the fetal sheep gonad. Biol Reprod. 2001, 65: 216-228. 10.1095/biolreprod65.1.216.CrossRefPubMed
39.
Juengel JL, Heath DA, Quirke LD, McNatty KP: Oestrogen receptor alpha and beta, androgen receptor and progesterone receptor mRNA and protein localisation within the developing ovary and in small growing follicles of sheep. Reproduction. 2006, 131: 81-92. 10.1530/rep.1.00704.CrossRefPubMed
40.
Clement TM, Anway MD, Uzumcu M, Skinner MK: Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes. Reproduction. 2007, 134: 455-72. 10.1530/REP-06-0341.CrossRefPubMed
41.
Houmard B, Small C, Yang L, Naluai-Cecchini T, Cheng E, Hassold T, Griswold M: Global gene expression in the human fetal testis and ovary. Biol Reprod. 2009, 81: 438-443. 10.1095/biolreprod.108.075747.PubMedCentralCrossRefPubMed
42.
43.
Garverick HA, Juengel JL, Smith P, Heath DA, Burkhart MN, Perry GA, Smith MF, McNatty KP: Development of the ovary and ontongeny of mRNA and protein for P450 aromatase (arom) and estrogen receptors (ER) alpha and beta during early fetal life in cattle. Anim Reprod Sci. 2010, 117: 24-33. 10.1016/j.anireprosci.2009.05.004.CrossRefPubMed
44.
Pandey DP, Picard D: miR-22 inhibits estrogen signaling by directly targeting the estrogen receptor alpha mRNA. Mol Cell Biol. 2009, 29: 3783-3790. 10.1128/MCB.01875-08.PubMedCentralCrossRefPubMed
45.
Heitman LH, Ijzerman AP: G protein-coupled receptors of the hypothalamic-pituitary-gonadal axis: a case for Gnrh, LH, FSH, and GPR54 receptor ligands. Med Res Rev. 2008, 28: 975-1011. 10.1002/med.20129.CrossRefPubMed
46.
Wang C, Prossnitz ER, Roy SK: G protein-coupled receptor 30 expression is required for estrogen stimulation of primordial follicle formation in the hamster ovary. Endocrinology. 2008, 149: 4452-4461. 10.1210/en.2008-0441.PubMedCentralCrossRefPubMed
47.
Ross DG, Bowles J, Hope M, Lehnert S, Koopman P: Profiles of gonadal gene expression in the developing bovine embryo. Sex Dev. 2009, 3: 273-283. 10.1159/000252791.CrossRefPubMed
48.
Pezzi V, Mathis JM, Rainey WE, Carr BR: Profiling transcript levels for steroidogenic enzymes in fetal tissues. J Steroid Biochem Mol Biol. 2003, 87: 181-189. 10.1016/j.jsbmb.2003.07.006.CrossRefPubMed
Metadata
Title
Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation
Authors
Katie J Torley
Juliano C da Silveira
Peter Smith
Russell V Anthony
DN Rao Veeramachaneni
Quinton A Winger
Gerrit J Bouma
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2011
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-9-2

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