Background <p>Mechanisms regulating the transition between two consecutive reproductive cycles are complex and remain poorly understood, mostly because they involve a dialog between the ovary and the central nervous system that is difficult to disentangle.</p> Results <p>In rainbow trout (<i>Oncorhynchus mykiss</i>), an iteroparous species spawning every year, removal of the eggs from the body cavity was used as a switch to trigger the onset of the next reproductive cycle. Changes in circulating miRNAs (c-miRNAs) levels in blood plasma and ovarian fluid were then monitored over time. Upon removal of the eggs from the body cavity, we observed the dramatic downregulation of the blood plasma levels of a single c-miRNA (miR-139-5p) that is predominantly expressed in the brain. In contrast, very distinct c-miRNAs profiles were observed in blood plasma when eggs are retained in the body cavity. Among plasma c-miRNAs showing dynamic changes with egg retention, miR-135c is strongly expressed in the brain and pituitary, while miR-457a is predominant in the post-ovulatory ovary. In addition, egg retention in the body cavity triggers a dramatic drop in ovarian fluid levels of miR-202-5p, a miRNA known to regulate egg production in fish.</p> Conclusions <p>Our observations reveal that the transition between two successive reproductive cycles involves a crosstalk between the eggs and the central system and that a single miRNA, miR-139, predominantly expressed in the brain, is associated with the onset of the next reproductive cycle. We identified possible miR-139-5p functional targets in rainbow trout and other iteroparous species that have been lost in semelparous salmonids. Our results offer new research perspectives to better understand the mechanisms triggering the next reproductive cycle in iteroparous fish species, including post-transcriptional regulations by miR-139 in the brain.</p>