Mating induces a rapid change in the Drosophila female’s physiology and behavior. The female increases her oviposition rate and avoids other males, and the morphology of her reproductive tissues changes rapidly. Mating-induced physiological responses are modulated by major changes in the expression profile of the female reproductive tissues. In the lower female reproductive tract (lower RT) miRNAs are involved in the regulation of this rapid response to mating. It has been demonstrated that miRNAs also regulate reproductive processes in mammals, such as mouse, pig and human. In human, for example, miRNAs regulate responses to gametes and modulate communication between the embryo and the maternal tract during implantation and pregnancy. miRNAs are highly conserved across species and thus might play a role in regulating the basic modules of reproduction which are broadly conserved.
To better understand the role of miRNAs in female reproductive success, we compared the miRNA expression profiles of unmated and mated Drosophila lower RTs with reported changes in miRNA profile of human endometrium in preparation for implantation to identify candidate miRNAs. We found two miRNAs, let-7a and miR-9a, whose expression was significantly altered in both organisms. Using a miR-sensor, we tested miRNA spatial localization in vivo in Drosophila females. We showed that the expression of miR-9a in Drosophila is reduced specifically in the spermathecal secretory cells (SSC) at 6h post-mating. This is the time when the reproductive tract is preparing for fertilization and egg laying. We then devised a miR-sensor system for use in vitro in mammalian cells to test in vitro the interaction of trophoblast spheroids (simulating the embryo) with human endometrial cells. We observed that the human endometrial cell line reacted to the presence of the trophoblast spheroids by increasing the expression of miR-9a. These results suggest that miR-9a might be an important miRNA for reproductive success as it seems to mediate the reproductive mechanisms of both species. Using our miR-sensor system, we further performed time lapse analysis to follow the interactions of the trophoblast and endometrial cells in real-time. We observed that the endometrial cells react to the presence of the trophoblast through miRNA-dependent and independent mechanisms. Understanding the role of conserved miRNAs in reproductive tissues will provide insight into mechanisms of female reproductive success.