Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes.
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.
Clement
Tracy M
TM
School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington 99164, USA.
Anway
Matthew D
MD
Uzumcu
Mehmet
M
Skinner
Michael K
MK
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
Reproduction. 2002 Oct;124(4):447-57
12361462
Genes Dev. 2000 Oct 15;14(20):2587-95
11040213
Biol Reprod. 1992 Jul;47(1):29-36
1637944
Development. 1991 Oct;113(2):613-24
1782869
Biol Reprod. 1992 Feb;46(2):233-45
1536899
Ann N Y Acad Sci. 1984;438:435-46
6598327
Nature. 1990 Jul 19;346(6281):240-4
1695712
Biol Reprod. 2002 Jun;66(6):1838-45
12021070
Exp Cell Res. 2005 Dec 10;311(2):177-91
16229834
Arch Anat Microsc Morphol Exp. 1980;69(4):297-318
7212698
Genomics. 2000 Dec 1;70(2):190-200
11112347
J Neurocytol. 2003 Jun-Sep;32(5-8):619-47
15034257
Dev Biol. 1998 Nov 15;203(2):323-33
9808783
Development. 2004 Aug;131(15):3627-36
15229180
Novartis Found Symp. 2002;244:240-9; discussion 249-57
11990795
Nat Genet. 1996 Apr;12(4):404-9
8630494
Biochem J. 2005 Dec 15;392(Pt 3):457-65
16131350
Am J Physiol Gastrointest Liver Physiol. 2005 Feb;288(2):G316-26
15358596
J Biol Chem. 2002 Jun 21;277(25):22314-9
11940591
Nature. 1990 Nov 29;348(6300):450-2
2247150
Mech Dev. 2000 Mar 15;92(1):89-103
10704890
Nature. 1990 Nov 29;348(6300):448-50
2247149
Mol Cell Biol. 1998 Apr;18(4):2230-9
9528794
J Biol Chem. 1990 Jul 25;265(21):12679-85
2165071
Anat Embryol (Berl). 1999 Mar;199(3):207-14
10068086
Biol Reprod. 2006 Jul;75(1):75-81
16540541
J Neurosci. 2003 May 1;23(9):3735-44
12736344
Ann Endocrinol (Paris). 1980 Nov-Dec;41(6):531-7
7247337
Nature. 1969 Dec 27;224(5226):1323-5
5359302
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7336-41
11390985
Mol Endocrinol. 1994 Jan;8(1):69-76
7512196
Am J Physiol. 1998 Jun;274(6):C1674-85
9611134
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11675-80
8876195
Biochim Biophys Acta. 2002 Apr 12;1574(3):391-8
11997109
PLoS Biol. 2006 Jun;4(6):e187
16700629
Biol Reprod. 2000 Jan;62(1):132-42
10611077
Braz J Med Biol Res. 1994 Aug;27(8):1855-63
7749374
J Clin Invest. 2005 Feb;115(2):233-6
15690080
Biol Reprod. 2006 May;74(5):978-83
16452457
Nature. 2004 Nov 11;432(7014):179-86
15510105
Dev Dyn. 2004 Jun;230(2):210-5
15162500
Development. 1993 Jan;117(1):273-81
8223251
Int J Androl. 2003 Jun;26(3):147-60
12755993
Trans Am Clin Climatol Assoc. 2003;114:51-63; discussion 64-5
12813911
Endocrinology. 2006 Jan;147(1):257-71
16195407
Development. 1990 Oct;110(2):521-8
2133553
Nat Genet. 2002 Nov;32(3):408-10
12368913
J Androl. 2001 Nov-Dec;22(6):944-52
11700858
Biol Reprod. 2005 Feb;72(2):492-501
15496517
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1016-21
12552091
J Biol Chem. 2005 Feb 18;280(7):5917-23
15590666
Mol Endocrinol. 2002 Dec;16(12):2780-92
12456799
Bioinformatics. 2004 Jun 12;20(9):1436-46
14962916
Genomics. 2006 Jul;88(1):52-64
16597497
Apoptosis. 2003 Aug;8(4):389-97
12815282
Mol Cell Biol. 1998 Nov;18(11):6653-65
9774680
Int J Dev Neurosci. 2001 Feb;19(1):21-35
11226752
Hum Mol Genet. 2006 Feb 1;15(3):417-31
16399799
Biol Reprod. 2003 Jun;68(6):2033-7
12606390
Hum Genet. 1981;58(1):59-63
7286994
PLoS Biol. 2006 Apr;4(4):e115
16602827
Cell. 1994 Dec 16;79(6):1111-20
8001137
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
9843981
Circulation. 2004 Sep 7;110(10):1231-5
15337698
Dev Biol. 2005 Nov 15;287(2):361-77
16214126
Fertil Steril. 1993 Nov;60(5):897-904
7693517
Peptides. 2005 Jun;26(6):1044-59
15911072
Mol Cell Endocrinol. 2005 Jan 31;230(1-2):87-93
15664455
Mol Cell Endocrinol. 2004 Oct 15;225(1-2):25-8
15451564
Dev Dyn. 2006 Sep;235(9):2292-300
16881057
Trends Genet. 2005 Nov;21(11):624-32
16169630
Exp Cell Res. 1998 Oct 10;244(1):230-8
9770365
Biol Reprod. 2000 Dec;63(6):1617-28
11090428
Cell. 2001 Mar 23;104(6):875-89
11290325
Dev Dyn. 2003 Aug;227(4):600-7
12889070
Mol Hum Reprod. 2002 May;8(5):419-25
11994538
Mol Cell Neurosci. 2005 Sep;30(1):58-66
16005638
Biol Reprod. 2005 Jan;72(1):241-55
15371273
J Neurosci. 2004 Dec 1;24(48):10816-25
15574732
Curr Biol. 1997 Dec 1;7(12):958-68
9382843
Exp Cell Res. 2001 Jul 15;267(2):225-32
11426941
Nature. 2003 Nov 20;426(6964):291-5
14628051
Histol Histopathol. 2006 Feb;21(2):125-30
16329036
FASEB J. 1996 Apr;10(5):598-614
8621059
Biol Reprod. 2002 Dec;67(6):1927-35
12444071
Nat Genet. 2005 Jul;37(7):710-7
15965475
Nat Genet. 2001 Jul;28(3):216-7
11431689
Biochem Biophys Res Commun. 2003 Aug 8;307(4):782-90
12878178
Novartis Found Symp. 2002;244:187-98; discussion 198-206, 253-7
11990791
Development. 2000 Jan;127(1):65-73
10654601
Dev Biol. 1999 Nov 15;215(2):208-20
10545231
Nature. 1998 Feb 19;391(6669):761-7
9486644
J Neurosci. 2003 Jul 30;23(17):6914-27
12890786
J Cell Biol. 2002 Jul 22;158(2):197-9
12135981
Biol Reprod. 2005 May;72(5):1205-17
15647457
Immunol Lett. 2006 Jan 15;102(1):1-9
16140393