MicroRNAs-140-5p/140-3p Modulate Leydig Cell Numbers in the Developing Mouse Testis1

Joanna Rakoczy, Selene L. Fernandez-Valverde, Evgeny A. Glazov, Elanor N. Wainwright, Tempei Sato, Shuji Takada, Alexander N. Combes, Darren J. Korbie, David Miller, Sean M. Grimmond, Melissa H. Little, Hiroshi Asahara, John S. Mattick, Ryan J. Taft, Dagmar Wilhelm

MicroRNAs (miRNAs) have been shown to play key regulatory roles in a range of biological processes, including cell differentiation and development. To identify miRNAs that participate in gonad differentiation, a fundamental and tightly regulated developmental process, we examined miRNA expression profiles at the time of sex determination and during the early fetal differentiation of mouse testes and ovaries using high-throughput sequencing. We identified several miRNAs that were expressed in a sexually dimorphic pattern, including several members of the let-7 family, miR-378, and miR-140-3p. We focused our analysis on the most highly expressed, sexually dimorphic miRNA, miR-140-3p, and found that both miR-140-3p and its more lowly expressed counterpart, the previously annotated guide strand, miR-140-5p, are testis enriched and expressed in testis cords. Analysis of the miR-140-5p/miR-140-3p-null mouse revealed a significant increase in the number of Leydig cells in the developing XY gonad, strongly suggesting an important role for miR-140-5p/miR-140-3p in testis differentiation in mouse.