Abstract
MicroRNAs are frequently organized into polycistronic clusters whose transcription is controlled by a single promoter. The miR-17-92 cluster is expressed in most embryonic and postnatal organs. It is a potent oncogene associated to several types of cancer and it is involved in several important developmental processes. In the testis, expression of the miR-17-92 cluster in the germ cells is necessary to maintain normal spermatogenesis. This cluster is also expressed in Sertoli cells (the somatic cells of the seminiferous tubules), which require miRNAs for correct cell development and survival. To study the possible role of miR-17-92 in Sertoli cell development and function and, in order to overcome the postnatal lethality of miR-17-92-/ mice, we conditionally deleted it in embryonic Sertoli cells shortly after the sex determination stage using an Amh-Cre allele. Mutant mice developed apparently normal testes and were fertile, but their testis transcriptomes contained hundreds of moderately deregulated genes, indicating that testis homeostasis is tightly controlled in mammals and that miR-17-92 expression in Sertoli cells contribute to maintain normal gene expression levels, but is unnecessary for testis development and function. Our results show that significant deregulation of hundreds of genes might have no functional consequences.
Highlights
Sertoli cells (SCs) are the epithelial supporting cells within the seminiferous tubules of mammalian adult testes
SC-specific ablation of Dicer resulted in abnormal testis development and spermatogenic failure, evidencing the importance of miRNAs in the differentiation and function of this cell type [14, 15]
Prompted by several studies showing the expression of members of the mir-17-92 cluster in SCs [12, 14, 16, 35], and knowing their relevant roles in other organs and disease conditions, we decided to induce the conditional ablation of this miRNA cluster in embryonic SCs shortly after testis differentiation
Summary
Sertoli cells (SCs) are the epithelial supporting cells within the seminiferous tubules of mammalian adult testes. Their main function is to sustain spermatogenesis by providing structural support, nursing and regulating the function of germ cells (GCs) via signaling molecules. They produce the seminiferous fluid and form the blood-testis barrier (BTB), an inter-SC. Burgos and grants from the Spanish Ministry of Science and Innovation (CGL2011-23368 and CGL2015-67108-P) to R. The authors would like to thank the Spanish Ministry of Science and Innovation for the “Ramon y Cajal” fellowship granted to F.D. Carmona (RYC-2014-16458) and the “FPU” PhD fellowship granted to A.
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