title: Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes.
abstract: Gene expression profiles during sex determination and gonadal differentiation were investigated to identify new potential regulatory factors. Embryonic day 13 (E13), E14, and E16 rat testes and ovaries were used for microarray analysis, as well as E13 testis organ cultures that undergo testis morphogenesis and develop seminiferous cords in vitro. A list of 109 genes resulted from a selective analysis for genes present in male gonadal development and with a 1.5-fold change in expression between E13 and E16. Characterization of these 109 genes potentially important for testis development revealed that cytoskeletal-associated proteins, extracellular matrix factors, and signaling factors were highly represented. Throughout the developmental period (E13-E16), sex-enriched transcripts were more prevalent in the male with 34 of the 109 genes having testis-enriched expression during sex determination. In ovaries, the total number of transcripts with a 1.5-fold change in expression between E13 and E16 was similar to the testis, but none of those genes were both ovary enriched and regulated during the developmental period. Genes conserved in sex determination were identified by comparing changing transcripts in the rat analysis herein, to transcripts altered in previously published mouse studies of gonadal sex determination. A comparison of changing mouse and rat transcripts identified 43 genes with species conservation in sex determination and testis development. Profiles of gene expression during E13-E16 rat testis and ovary development are presented and candidate genes for involvement in sex determination and testis differentiation are identified. Analysis of cellular pathways did not reveal any specific pathways involving multiple candidate genes. However, the genes and gene network identified influence numerous cellular processes with cellular differentiation, proliferation, focal contact, RNA localization, and development being predominant.
authors: School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington 99164, USA.
authors: Tracy M
authors: TM
authors: Clement
authors: Matthew D
authors: MD
authors: Anway
authors: Mehmet
authors: M
authors: Uzumcu
authors: Michael K
authors: MK
authors: Skinner
mesh_terms: D000818:Animals; D019295:Computational Biology; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D008297:Male; D009024:Morphogenesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D010053:Ovary / Q000196:embryology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019849:Sex Determination Processes; D012733:Sex Differentiation; D013737:Testis / Q000196:embryology*; D014158:Transcription, Genetic / Q000502:physiology
references: Reproduction. 2002 Oct;124(4):447-57
references: 12361462
references: Genes Dev. 2000 Oct 15;14(20):2587-95
references: 11040213
references: Biol Reprod. 1992 Jul;47(1):29-36
references: 1637944
references: Development. 1991 Oct;113(2):613-24
references: 1782869
references: Biol Reprod. 1992 Feb;46(2):233-45
references: 1536899
references: Ann N Y Acad Sci. 1984;438:435-46
references: 6598327
references: Nature. 1990 Jul 19;346(6281):240-4
references: 1695712
references: Biol Reprod. 2002 Jun;66(6):1838-45
references: 12021070
references: Exp Cell Res. 2005 Dec 10;311(2):177-91
references: 16229834
references: Arch Anat Microsc Morphol Exp. 1980;69(4):297-318
references: 7212698
references: Genomics. 2000 Dec 1;70(2):190-200
references: 11112347
references: J Neurocytol. 2003 Jun-Sep;32(5-8):619-47
references: 15034257
references: Dev Biol. 1998 Nov 15;203(2):323-33
references: 9808783
references: Development. 2004 Aug;131(15):3627-36
references: 15229180
references: Novartis Found Symp. 2002;244:240-9; discussion 249-57
references: 11990795
references: Nat Genet. 1996 Apr;12(4):404-9
references: 8630494
references: Biochem J. 2005 Dec 15;392(Pt 3):457-65
references: 16131350
references: Am J Physiol Gastrointest Liver Physiol. 2005 Feb;288(2):G316-26
references: 15358596
references: J Biol Chem. 2002 Jun 21;277(25):22314-9
references: 11940591
references: Nature. 1990 Nov 29;348(6300):450-2
references: 2247150
references: Mech Dev. 2000 Mar 15;92(1):89-103
references: 10704890
references: Nature. 1990 Nov 29;348(6300):448-50
references: 2247149
references: Mol Cell Biol. 1998 Apr;18(4):2230-9
references: 9528794
references: J Biol Chem. 1990 Jul 25;265(21):12679-85
references: 2165071
references: Anat Embryol (Berl). 1999 Mar;199(3):207-14
references: 10068086
references: Biol Reprod. 2006 Jul;75(1):75-81
references: 16540541
references: J Neurosci. 2003 May 1;23(9):3735-44
references: 12736344
references: Ann Endocrinol (Paris). 1980 Nov-Dec;41(6):531-7
references: 7247337
references: Nature. 1969 Dec 27;224(5226):1323-5
references: 5359302
references: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7336-41
references: 11390985
references: Mol Endocrinol. 1994 Jan;8(1):69-76
references: 7512196
references: Am J Physiol. 1998 Jun;274(6):C1674-85
references: 9611134
references: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11675-80
references: 8876195
references: Biochim Biophys Acta. 2002 Apr 12;1574(3):391-8
references: 11997109
references: PLoS Biol. 2006 Jun;4(6):e187
references: 16700629
references: Biol Reprod. 2000 Jan;62(1):132-42
references: 10611077
references: Braz J Med Biol Res. 1994 Aug;27(8):1855-63
references: 7749374
references: J Clin Invest. 2005 Feb;115(2):233-6
references: 15690080
references: Biol Reprod. 2006 May;74(5):978-83
references: 16452457
references: Nature. 2004 Nov 11;432(7014):179-86
references: 15510105
references: Dev Dyn. 2004 Jun;230(2):210-5
references: 15162500
references: Development. 1993 Jan;117(1):273-81
references: 8223251
references: Int J Androl. 2003 Jun;26(3):147-60
references: 12755993
references: Trans Am Clin Climatol Assoc. 2003;114:51-63; discussion 64-5
references: 12813911
references: Endocrinology. 2006 Jan;147(1):257-71
references: 16195407
references: Development. 1990 Oct;110(2):521-8
references: 2133553
references: Nat Genet. 2002 Nov;32(3):408-10
references: 12368913
references: J Androl. 2001 Nov-Dec;22(6):944-52
references: 11700858
references: Biol Reprod. 2005 Feb;72(2):492-501
references: 15496517
references: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1016-21
references: 12552091
references: J Biol Chem. 2005 Feb 18;280(7):5917-23
references: 15590666
references: Mol Endocrinol. 2002 Dec;16(12):2780-92
references: 12456799
references: Bioinformatics. 2004 Jun 12;20(9):1436-46
references: 14962916
references: Genomics. 2006 Jul;88(1):52-64
references: 16597497
references: Apoptosis. 2003 Aug;8(4):389-97
references: 12815282
references: Mol Cell Biol. 1998 Nov;18(11):6653-65
references: 9774680
references: Int J Dev Neurosci. 2001 Feb;19(1):21-35
references: 11226752
references: Hum Mol Genet. 2006 Feb 1;15(3):417-31
references: 16399799
references: Biol Reprod. 2003 Jun;68(6):2033-7
references: 12606390
references: Hum Genet. 1981;58(1):59-63
references: 7286994
references: PLoS Biol. 2006 Apr;4(4):e115
references: 16602827
references: Cell. 1994 Dec 16;79(6):1111-20
references: 8001137
references: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references: 9843981
references: Circulation. 2004 Sep 7;110(10):1231-5
references: 15337698
references: Dev Biol. 2005 Nov 15;287(2):361-77
references: 16214126
references: Fertil Steril. 1993 Nov;60(5):897-904
references: 7693517
references: Peptides. 2005 Jun;26(6):1044-59
references: 15911072
references: Mol Cell Endocrinol. 2005 Jan 31;230(1-2):87-93
references: 15664455
references: Mol Cell Endocrinol. 2004 Oct 15;225(1-2):25-8
references: 15451564
references: Dev Dyn. 2006 Sep;235(9):2292-300
references: 16881057
references: Trends Genet. 2005 Nov;21(11):624-32
references: 16169630
references: Exp Cell Res. 1998 Oct 10;244(1):230-8
references: 9770365
references: Biol Reprod. 2000 Dec;63(6):1617-28
references: 11090428
references: Cell. 2001 Mar 23;104(6):875-89
references: 11290325
references: Dev Dyn. 2003 Aug;227(4):600-7
references: 12889070
references: Mol Hum Reprod. 2002 May;8(5):419-25
references: 11994538
references: Mol Cell Neurosci. 2005 Sep;30(1):58-66
references: 16005638
references: Biol Reprod. 2005 Jan;72(1):241-55
references: 15371273
references: J Neurosci. 2004 Dec 1;24(48):10816-25
references: 15574732
references: Curr Biol. 1997 Dec 1;7(12):958-68
references: 9382843
references: Exp Cell Res. 2001 Jul 15;267(2):225-32
references: 11426941
references: Nature. 2003 Nov 20;426(6964):291-5
references: 14628051
references: Histol Histopathol. 2006 Feb;21(2):125-30
references: 16329036
references: FASEB J. 1996 Apr;10(5):598-614
references: 8621059
references: Biol Reprod. 2002 Dec;67(6):1927-35
references: 12444071
references: Nat Genet. 2005 Jul;37(7):710-7
references: 15965475
references: Nat Genet. 2001 Jul;28(3):216-7
references: 11431689
references: Biochem Biophys Res Commun. 2003 Aug 8;307(4):782-90
references: 12878178
references: Novartis Found Symp. 2002;244:187-98; discussion 198-206, 253-7
references: 11990791
references: Development. 2000 Jan;127(1):65-73
references: 10654601
references: Dev Biol. 1999 Nov 15;215(2):208-20
references: 10545231
references: Nature. 1998 Feb 19;391(6669):761-7
references: 9486644
references: J Neurosci. 2003 Jul 30;23(17):6914-27
references: 12890786
references: J Cell Biol. 2002 Jul 22;158(2):197-9
references: 12135981
references: Biol Reprod. 2005 May;72(5):1205-17
references: 15647457
references: Immunol Lett. 2006 Jan 15;102(1):1-9
references: 16140393