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), sexenriched 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. Reproduction (2007) 134 455-472

Uncovering Gene Regulatory Networks During Mouse Fetal Germ Cell Development

“…A number of transcriptomic analyses have investigated gene networks underlying sex determination and gonad development, but those analyses were focused mainly on the somatic cell compartment of the differentiating gonads [23] and tended to use mRNA derived from whole gonads to uncover gene networks underlying this process in the mouse [28], rat [47], or human [27]. While those datasets provide information regarding genes expressed in germ cells, they do not make it possible to associate gene expression within any specific cell type in the developing gonad.…”

SRY Directly Regulates the Neurotrophin 3 Promoter During Male Sex Determination and Testis Development in Rats1

“…The expression of Ntf3 and Sry during embryonic testis development was also determined using microarray analysis [27]. The expression of Sry was highest at rat Embryonic Day SRY REGULATES Ntf3 PROMOTER 279 13, with Ntf3 following at E14 (Fig.…”

“…2. Ntf3 and Sry expression profiles during embryonic testis development in the rat from a microarray analysis data set [27]. Relative expression versus embryonic day of development is presented.…”

Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary

“…To achieve a more comprehensive view of the molecular mechanisms of mammalian sex determination and early gonad organogenesis, genome-wide technologies such as microarrays have been used [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] . To study the roles of Wnt-4 in the ovarian vasculature [18] and in the differentiation of granulosa cells [19] such method was carried on, although the molecular mechanisms by which Wnt-4 controls early sexual development remain poorly characterized.…”