Kisspeptin Influences the Reproductive Axis and Circulating Levels of microRNAs in Senegalese Sole

Abstract

Kisspeptin regulates puberty and reproduction onset, acting upstream of the brain–pituitary–gonad (HPG) axis. This study aimed to test a kisspeptin-based hormonal therapy on cultured Senegalese sole (G1) breeders, known to have reproductive dysfunctions. A single intramuscular injection of KISS2-10 decapeptide (250 µg/kg) was tested in females and males during the reproductive season, and gonad maturation, sperm motility, plasma levels of gonadotropins (Fsh and Lh) and sex steroids (11-ketotestosterone, testosterone and estradiol), as well as changes in small non-coding RNAs (sncRNAs) in plasma, were investigated. Fsh, Lh, and testosterone levels increased after kisspeptin injection in both sexes, while sperm analysis did not show differences between groups. Let7e, miR-199a-3p and miR-100-5p were differentially expressed in females, while miR-1-3p miRNA was up-regulated in kisspeptin-treated males. In silico prediction of mRNAs targeted by miRNAs revealed that kisspeptin treatment might affect paracellular transporters, regulate structural and functional polarity of cells, neural networks and intracellular trafficking in Senegalese sole females; also, DNA methylation and sphingolipid metabolism might be altered in kisspeptin-treated males. Results demonstrated that kisspeptin stimulated gonadotropin and testosterone secretion in both sexes and induced an unanticipated alteration of plasma miRNAs, opening new research venues to understand how this neuropeptide impacts in fish HPG axis.

Kisspeptin-10 Promotes Progesterone Synthesis in Bovine Ovarian Granulosa Cells via Downregulation of microRNA-1246

“…Recently, it has been widely accepted that miRNAs were involved in the regulation of P4 synthesis in GCs [ 38 ]. A recent study showed that kp-10 stimulated Senegalese soles’ gonadotropin and testosterone synthesis and induced changes in its plasma miRNAs [ 39 ]. Similarly, we found that kp-10 decreased miR-1246 expression in BGCs.…”

Integrative Analysis of miRNA-mRNA in Ovarian Granulosa Cells Treated with Kisspeptin in Tan Sheep

“…Our research group also showed that kisspeptin could promote the secretion of steroid hormones and cell proliferation in ovarian granulosa cells of Tan sheep in vitro (unpublished data), but the specific molecular mechanism remains unclear. Recent studies have indicated that kisspeptin-10 could significantly change the expression of circulating miRNAs (let-7e, miR-100-5p, and others) obtained from the plasma of gonads of Senegalese Sole, affecting their reproduction [ 26 ]. Kisspeptin-10 has been reported to induce progesterone synthesis in bovine granulosa cells by regulating the expression of miR-146-targeted StAR genes [ 24 ].…”

Overview and New Insights Into the Diversity, Evolution, Role, and Regulation of Kisspeptins and Their Receptors in Teleost Fish

“…However, Kiss2 is more effective than Kiss1 in triggering gonadotropin secretion in this species ( 46 ). Similarly, intramuscular injection of Kiss2 stimulates secretion of Fsh and Lh in Senegalese sole of both sexes ( 94 ). Moreover, a differential and gonadal stage-dependent roles of kisspeptin on Lh release was observed in hybrid bass: Kiss1 increases plasma LH levels during gonadal recrudescence in vivo , whereas Kiss2 stimulates the release of LH during at pre-puberty and gonadal recrudescence ( 17 ).…”

“…Similarly, plasma levels of 11-KT in males and E 2 in females are significantly increased in immature Nile tilapia treated with Kiss2, and Kiss2 apparently accelerates the process of spermatogenesis ( 92 ). Recently, Kiss2 was shown to stimulate T secretion in both sexes of Senegalese sole ( 94 ). All these data suggest an effect on the gonads, probably mediated by gonadotropins, but a direct effect of kisspeptins on the gonads have been less considered.…”