Abstract
BackgroundGonadal 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.MethodsWe 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.ResultsExpression 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.ConclusionsBased on our results we postulate that gene expression networks underlying fetal gonadal development are regulated by miRNAs.
Highlights
Gonadal differentiation in the mammalian fetus involves a complex dose-dependent genetic network
At GD42, when testicular cords develop in XY gonads (Figure 1), 24 miRNAs exhibited a sexual dimorphic expression pattern with at least 2 fold difference (Table 1)
In addition to identifying miRNAs exhibiting sexual dimorphic expression patterns, relative expression level of miRNAs was examined during development within fetal ovaries and fetal testes by comparing miRNA expression in GD42 and GD75 gonads
Summary
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). Mammalian fetal gonadal differentiation is a developmental process involving a dose dependent balance between promoting and antagonizing factors. The testicular developmental pathway involves genetic networks both promoting testis development and preventing ovarian development and vice versa [1,2]. Small non-coding RNA molecules called microRNAs (miRNAs) are ~22 nt cytoplasmic RNAs that regulate gene expression and function in many tissues [15,16,17].
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