Biology subjects

Lagarde, C.

Publications and source records attributed to Lagarde, C..

2 recordsLinked to original sources

bioRxiv2026

miR-202 drives medaka fertility by targeting antagonistic Yap-dependent transcriptional regulators tead3b and vgll4b in a sex-dependent manner

How miRNAs can sometimes drive major organism-level phenotypes by targeting a single gene and by triggering limited changes in mRNA levels remains poorly understood, especially in vertebrates. In medaka, the knockout of miR-202-5p, a gonad-specific miRNA in vertebrates, leads to impaired male and female fertility, including drastically reduced egg production and low developmental success. Here we show that miR-202-5p drives gamete formation by targeting antagonist Yap-dependent transcriptional regulators tead3b and vgll4b in a sex-dependent manner. Disruption of the miR-202-5p binding site in the 3UTR of tead3b, but not vgll4b, results in a significant decrease in female fertility. In contrast, disrupting miR-202-5p target site in the 3UTR of vgll4b, but not tead3b, results in impaired male fertility. In females, 3D ovary imaging and RNA-seq analysis of isolated ovarian follicles revealed that disrupting miR-202-5p binding to the 3 UTR of tead3b results in a polycystic ovarian syndrome (PCOS)-like phenotype and the expression of many PCOS-associated marker, including androgen signaling and estrogen metabolism genes. In males, disrupting miR-202-5p binding to the 3UTR of vgll4b triggers severe phenotypes, including reduced sperm motility and abnormal testicular development. No effects on sex ratio were observed, indicating that miR-202-5p drives gamete formation by regulating mechanisms acting down-stream of the sex-determining cascade. The analysis of miR-202-5p target sites in 3 UTRs suggests long-term conservation of antagonistic TEAD and VGLL targeting across vertebrate species, including mammals. Together, our results show that miR-202-5p drives fertility by leveraging antagonistic Yap-dependent transcriptional regulators in a sex dependent manner.

genetics↗

bioRxiv2025

Circulating microRNAs reveal egg-brain crosstalk and a brain-specific microRNA linked to the onset of the next reproductive cycle in iteroparous salmonids

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. In rainbow trout (Oncorhynchus mykiss), 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 down regulation 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 postovulatory 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. 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.

physiology↗