Mouse ovary developmental RNA and protein markers from gene expression profiling.

To identify genes involved in morphogenetic events during mouse ovary development, we started with microarray analyses of whole organ RNA. Transcripts for 60% of the 15,000 gene NIA panel were detected, and about 2000 were differentially expressed in nascent newborn compared to adult ovary. Highly differentially expressed transcripts included noncoding RNAs and newly detected genes involved in transcription regulation and signal transduction. The phased pattern of newborn mouse ovary differentiation allowed us to (1) extend information on activity and stage specificity of cell type-specific genes; and (2) generate a list of candidate genes involved in primordial follicle formation, including podocalyxin (Podxl), PDGFR-beta, and a follistatin-domain-encoding gene Flst1. Oocyte-specific transcripts included many (e.g., Deltex2, Bicd2, and Zfp37) enriched in growing oocytes, as well as a novel family of untranslated RNA's (RLTR10) that is selectively expressed in early stage follicles. The results indicate that global expression profiling of whole organ RNA provides sensitive first-line information about ovarian histogenesis for which no in vitro cell models are currently available.

[1]  Martin M Matzuk,et al.  NOBOX Deficiency Disrupts Early Folliculogenesis and Oocyte-Specific Gene Expression , 2004, Science.

[2]  S. Ojeda,et al.  Nerve growth factor is required for early follicular development in the mammalian ovary. , 2001, Endocrinology.

[3]  C. Hoogenraad,et al.  Mammalian Golgi‐associated Bicaudal‐D2 functions in the dynein–dynactin pathway by interacting with these complexes , 2001, The EMBO journal.

[4]  J. Smith,et al.  ROLE OF FETAL FOLLICULAR CELLS IN MEIOSIS OF MAMMALIAN OOECYTES. , 1964, Cytogenetics.

[5]  D. Price,et al.  The role of neurotrophin receptors in female germ-cell survival in mouse and human , 2003, Development.

[6]  K. Park,et al.  Expression of an intracisternal A-particle-like element in rat ovary. , 2000, Biochemical and biophysical research communications.

[7]  R. Schiff,et al.  Transcriptional activation of mouse retrotransposons in vivo: specific expression in steroidogenic cells in response to trophic hormones. , 1991, Genes & development.

[8]  T. Graf,et al.  Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin , 2001, The Journal of experimental medicine.

[9]  H. Peters,et al.  The development of the mouse ovary from birth to maturity. , 1969, Acta endocrinologica.

[10]  R. Rodgers,et al.  Dynamics of the membrana granulosa during expansion of the ovarian follicular antrum , 2001, Molecular and Cellular Endocrinology.

[11]  R. McIsaac,et al.  Gpbox (Psx2), a homeobox gene preferentially expressed in female germ cells at the onset of sexual dimorphism in mice. , 2000, Developmental biology.

[12]  Katrin Anlag,et al.  The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance , 2004, Development.

[13]  B. Hogan,et al.  Developmental expression of renal angiotensin II receptor genes in the mouse. , 1995, Kidney international.

[14]  N. Galjart,et al.  Zfp-37 is a member of the KRAB zinc finger gene family and is expressed in neurons of the developing and adult CNS. , 1996, Genomics.

[15]  Zoran Galic,et al.  Controlling false-negative errors in microarray differential expression analysis: a PRIM approach. , 2003, Bioinformatics.

[16]  T. Saruta,et al.  Regulation of differential COUP-TF-coregulator interactions in adrenal cortical steroidogenesis , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[17]  D. Schlessinger,et al.  EDA targets revealed by skin gene expression profiles of wild-type, Tabby and Tabby EDA-A1 transgenic mice. , 2002, Human molecular genetics.

[18]  M. Soares,et al.  Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development. , 2000, Human molecular genetics.

[19]  L. Nelson,et al.  Mater encodes a maternal protein in mice with a leucine-rich repeat domain homologous to porcine ribonuclease inhibitor , 2000, Mammalian Genome.

[20]  Martin M Matzuk,et al.  Analysis of Ovarian Gene Expression in Follicle-Stimulating Hormone β Knockout Mice. , 2001, Endocrinology.

[21]  J. Sanes,et al.  Sex-specific localization of laminin α5 chain in the differentiating rat testis and ovary , 1999 .

[22]  M. Gassmann,et al.  Tissue-specific expression of a FMR1/β-galactosidase fusion gene in transgenic mice , 1995 .

[23]  U. Vitt,et al.  In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. , 2000, Endocrinology.

[24]  J. Claverie,et al.  The significance of digital gene expression profiles. , 1997, Genome research.

[25]  N. Copeland,et al.  Identification of podocalyxin-like protein 1 as a novel cell surface marker for hemangioblasts in the murine aorta-gonad-mesonephros region. , 1999, Immunity.

[26]  C. Westphal,et al.  Atm-dependent interactions of a mammalian Chk1 homolog with meiotic chromosomes , 1997, Current Biology.

[27]  A. Mclaren,et al.  Germ and somatic cell lineages in the developing gonad , 2000, Molecular and Cellular Endocrinology.

[28]  L. Campagnolo,et al.  Expression and role of PDGF-BB and PDGFR-β during testis morphogenesis in the mouse embryo , 2004, Journal of Cell Science.

[29]  A. Appert,et al.  Patterns of keratins 8, 18 and 19 during gonadal differentiation in the mouse: sex- and time-dependent expression of keratin 19. , 1998, Differentiation; research in biological diversity.

[30]  V. Ferrario,et al.  Morphometric study of the human ovary during compartmentalization , 1993, The Anatomical record.

[31]  K. Nose,et al.  Cloning from a mouse osteoblastic cell line of a set of transforming-growth-factor-beta 1-regulated genes, one of which seems to encode a follistatin-related polypeptide. , 1993, European journal of biochemistry.

[32]  M. Matzuk,et al.  Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. , 2001, Molecular endocrinology.

[33]  C. Disteche,et al.  Identification of ZFR, an ancient and highly conserved murine chromosome-associated zinc finger protein. , 1999, Gene.

[34]  Lukasz Huminiecki,et al.  In Silico Cloning of Novel Endothelial-Specific Genes , 2000 .

[35]  A. McMahon,et al.  Female development in mammals is regulated by Wnt-4 signalling , 1999, Nature.

[36]  H. Okano,et al.  Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis , 2001, International Journal of Developmental Neuroscience.

[37]  S. Wölfl,et al.  Ranking: a closer look on globalisation methods for normalisation of gene expression arrays. , 2002, Nucleic acids research.

[38]  Serafino Pantano,et al.  Emx2 developmental expression in the primordia of the reproductive and excretory systems , 1997, Anatomy and Embryology.

[39]  D. Schlessinger,et al.  Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development. , 2004, Human molecular genetics.

[40]  D. Schlessinger,et al.  The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome , 2001, Nature Genetics.

[41]  J. Brosius,et al.  RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements. , 1999, Gene.

[42]  T. Heidmann,et al.  Germ line-specific expression of intracisternal A-particle retrotransposons in transgenic mice , 1996, Molecular and cellular biology.

[43]  George Matcuk,et al.  Identification of endothelial cell genes by combined database mining and microarray analysis. , 2003, Physiological genomics.

[44]  R. Gosden The vocabulary of the egg , 1996, Nature.

[45]  M. Byrne,et al.  Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. , 2002, Molecular endocrinology.

[46]  Y. Sugisaki,et al.  Identification of MG-160, a FGF binding medial Golgi sialoglycoprotein, in brain tumors: an index of malignancy in astrocytomas. , 2003, International journal of oncology.

[47]  L. Liang,et al.  FIGalpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes. , 1997, Development.

[48]  Paolo Sassone-Corsi,et al.  The intracellular localisation of TAF7L, a paralogue of transcription factor TFIID subunit TAF7, is developmentally regulated during male germ-cell differentiation , 2003, Journal of Cell Science.

[49]  M. Ko,et al.  Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[50]  A. Orth,et al.  Large-scale analysis of the human and mouse transcriptomes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[51]  M. Fagiolini,et al.  Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia. , 2003, Genome research.

[52]  M. Ono Molecular cloning and long terminal repeat sequences of human endogenous retrovirus genes related to types A and B retrovirus genes , 1986, Journal of virology.

[53]  D. Tuan,et al.  The LTR enhancer of ERV-9 human endogenous retrovirus is active in oocytes and progenitor cells in transgenic zebrafish and humans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[54]  M. Matzuk,et al.  Mouse models of ovarian failure. , 1998, Reviews of reproduction.

[55]  A. Kispert,et al.  Female Development in Mammals is Regulated by Wnt-4-Signaling , 1999 .

[56]  A. Trounson,et al.  Identification and characterisation of known and novel transcripts expressed during the final stages of human oocyte maturation , 2002, Molecular reproduction and development.

[57]  D G Wilkinson,et al.  Detection of messenger RNA by in situ hybridization to tissue sections and whole mounts. , 1993, Methods in enzymology.

[58]  R. Rajah,et al.  The changing architecture of the neonatal rat ovary during histogenesis , 1992, Developmental dynamics : an official publication of the American Association of Anatomists.

[59]  D. Wolgemuth,et al.  Zfp-37, a new murine zinc finger encoding gene, is expressed in a developmentally regulated pattern in the male germ line. , 1992, Nucleic acids research.

[60]  S. Martin,et al.  Tightly regulated, developmentally specific expression of the first open reading frame from LINE-1 during mouse embryogenesis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[61]  A. Mohd-Sarip,et al.  Expression pattern and cellular distribution of the murine homologue of AF10. , 1998, Biochimica et biophysica acta.

[62]  I. Hughes,et al.  Tescalcin, a novel gene encoding a putative EF-hand Ca2+-binding protein, Col9a3, and Renin are expressed in the mouse testis during the early stages of gonadal differentiation , 2001 .

[63]  S. Ojeda,et al.  Expression of neurotrophins and their receptors in the mammalian ovary is developmentally regulated: changes at the time of folliculogenesis. , 1995, Endocrinology.

[64]  K. Lueders,et al.  The intracisternal A-particle gene family: structure and functional aspects. , 1988, Advances in cancer research.

[65]  R. Canipari Oocyte--granulosa cell interactions. , 2000, Human reproduction update.

[66]  Geppino Falco,et al.  Transcriptome Analysis of Mouse Stem Cells and Early Embryos , 2003, PLoS biology.

[67]  A. Levine,et al.  Germ Cell Expression of an Isolated Human Endogenous Retroviral Long Terminal Repeat of the HERV-K/HTDV Family in Transgenic Mice , 1999, Journal of Virology.

[68]  K. Wertz,et al.  Large-scale screen for genes involved in gonad development , 2000, Mechanisms of Development.

[69]  B. Hogan,et al.  Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. , 1999, Molecular cell.

[70]  D. Kelly,et al.  Angiotensin II influences ovarian follicle development in the transgenic (mRen-2)27 and Sprague-Dawley rat. , 2004, The Journal of endocrinology.

[71]  T. Magnaldo,et al.  Galectin-7, a marker of all types of stratified epithelia. , 1998, Differentiation; research in biological diversity.

[72]  Z. Rosenwaks,et al.  Application of complementary DNA microarray (DNA chip) technology in the study of gene expression profiles during folliculogenesis. , 2000, Fertility and sterility.

[73]  John D. Storey,et al.  Statistical significance for genomewide studies , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[74]  A. Byskov,et al.  The cortex-medulla oocyte growth pattern is organized during fetal life: an in-vitro study of the mouse ovary. , 1997, Molecular human reproduction.

[75]  Kit S Lam,et al.  From combinatorial chemistry to chemical microarray. , 2002, Current opinion in chemical biology.

[76]  J. Findlay,et al.  Differential responses of post-natal rat ovarian cells to FSH and activin , 1996, Molecular and Cellular Endocrinology.

[77]  J. Cooke,et al.  Cloning and early dorsal axial expression of Flik, a chick follistatin-related gene: evidence for involvement in dorsalization/neural induction. , 1996, Developmental biology.

[78]  Taesung Park,et al.  Evaluation of normalization methods for microarray data , 2003 .

[79]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[80]  M. Matzuk,et al.  Functional analysis of oocyte-expressed genes using transgenic models , 2002, Molecular and Cellular Endocrinology.

[81]  J. Tilly,et al.  Programmed cell death in the ovary: insights and future prospects using genetic technologies. , 2001, Molecular endocrinology.

[82]  H. Schöler,et al.  Derivation of Oocytes from Mouse Embryonic Stem Cells , 2003, Science.

[83]  S. Soyal,et al.  FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation. , 2000, Development.

[84]  M. Ruggiu,et al.  The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis , 1997, Nature.

[85]  Tomoko Kaneko,et al.  Corrigendum: Germline stem cells and follicular renewal in the postnatal mammalian ovary , 2004, Nature.

[86]  C. Rodeck,et al.  Identification of genes expressed in human primordial germ cells at the time of entry of the female germ line into meiosis. , 1999, Molecular human reproduction.

[87]  Yong Lin,et al.  DNA microarray analysis of the expression profiles of luteinized granulosa cells as a function of ovarian reserve. , 2002, Fertility and sterility.

[88]  B. Hogan,et al.  Embryonic expression of a haematopoietic growth factor encoded by the SI locus and the ligand for c-kit , 1990, Nature.

[89]  J. Yang,et al.  Oligonucleotide Microarray Data Distribution And Normalization , 2002, JCIS.

[90]  D. Wolgemuth,et al.  Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis. , 1999, Endocrinology.

[91]  K. Tamura,et al.  Use of stepwise subtraction to comprehensively isolate mouse genes whose transcription is up‐regulated during spermiogenesis , 2002, EMBO reports.

[92]  K. Manova,et al.  Gonadal expression of c-kit encoded at the W locus of the mouse. , 1990, Development.

[93]  J. Dean,et al.  Oocyte-specific genes regulate follicle formation, fertility and early mouse development. , 2002, Journal of reproductive immunology.

[94]  David F. Albertini,et al.  Growth differentiation factor-9 is required during early ovarian folliculogenesis , 1996, Nature.

[95]  M. Matzuk,et al.  Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. , 1999, Molecular endocrinology.

[96]  F. Shi,et al.  Relationship between FoxO1 protein levels and follicular development, atresia, and luteinization in the rat ovary. , 2003, The Journal of endocrinology.