Gnrh2 maintains reproduction in fasting zebrafish through dynamic neuronal projection changes and regulation of gonadotropin synthesis, oogenesis, and reproductive behaviors

Abstract

Restricted food intake, either from lack of food sources or endogenous fasting, during reproductive periods is a widespread phenomenon across the animal kingdom. Considering previous studies show the canonical upstream regulator of reproduction in vertebrates, the hypothalamic Gonadotropin-releasing hormone (Gnrh), is inhibited in some fasting animals, we sought to understand the neuroendocrine control of reproduction in fasted states. Here, we explore the roles of the midbrain neuropeptide, Gnrh2, in inducing reproduction via its pituitary prevalence, gonadotropin synthesis, gametogenesis, and reproductive outputs in the zebrafish model undergoing different feeding regimes. We discovered a fasting-induced four-fold increase in length and abundance of Gnrh2 neuronal projections to the pituitary and in close proximity to gonadotropes, whereas the hypothalamic Gnrh3 neurons are reduced by six-fold in length. Subsequently, we analyzed the functional roles of Gnrh2 by comparing reproductive parameters of a Gnrh2-depleted model, gnrh2−/−, to wild-type zebrafish undergoing different feeding conditions. We found that Gnrh2 depletion in fasted states compromises spawning success, with associated decreases in gonadotropin production, oogenesis, fecundity, and male courting behavior. Gnrh2 neurons do not compensate in other circumstances by which Gnrh3 is depleted, such as in gnrh3−/− zebrafish, implying that Gnrh2 acts to induce reproduction specifically in fasted zebrafish.

Chemogenetic Depletion of Hypophysiotropic GnRH Neurons Does Not Affect Fertility in Mature Female Zebrafish

“…Finally, pituitary GnRH2 protein content is unchanged in GnRH3 neuron-ablated females, suggesting that GnRH2 did not assume the role of GnRH3 in LH secretion. This result can be supported by the findings that female GnRH2 mutants ( gnrh2 −/− ) and female mutants that lack all GnRHs ( gnrh2 −/− ; gnrh3 −/− ) also maintain normal fertility in zebrafish [ 70 , 71 ]. In WT zebrafish, the number of GnRH2 neurons projecting to the pituitaries and reaching the LH gonadotropes are lower relative to those of GnRH3 neurons [ 70 ].…”

“…This result can be supported by the findings that female GnRH2 mutants ( gnrh2 −/− ) and female mutants that lack all GnRHs ( gnrh2 −/− ; gnrh3 −/− ) also maintain normal fertility in zebrafish [ 70 , 71 ]. In WT zebrafish, the number of GnRH2 neurons projecting to the pituitaries and reaching the LH gonadotropes are lower relative to those of GnRH3 neurons [ 70 ]. Therefore, unlike what is reported after fasting [ 70 ], the reduction in the number of GnRH3 neuronal projections to the pituitary may not provoke the plasticity of GnRH2 neurons.…”

“…In WT zebrafish, the number of GnRH2 neurons projecting to the pituitaries and reaching the LH gonadotropes are lower relative to those of GnRH3 neurons [ 70 ]. Therefore, unlike what is reported after fasting [ 70 ], the reduction in the number of GnRH3 neuronal projections to the pituitary may not provoke the plasticity of GnRH2 neurons.…”

Cannabidiol Inhibited Reproductive Ability of Zebrafish (Danio Rerio) with Gender-Dependent Manner

“…Studies have shown that GnRH depletion is positively correlated with a reduction in GSI and gonadotropin production, further affecting oogenesis, spawning success, fecundity, and male courting behaviour (Marvel et al, 2021). LH and FSH also positively affect the development of zebra sh gonads.…”

Tachykinins, new players in the control of reproduction and food intake: A comparative review in mammals and teleosts

“…In a teleost, the zebrafish, the knockout of either tac3a, tac3b, or both does not disrupt the reproduction (spermatogenesis and folliculogenesis are not impaired) (163). The impact of tac3 gene mutation should be now studied in other teleost species, as knockout studies of reproductive genes such as the different types of gnrh [gnrh3 (164); gnrh2 (165)] and kiss [kiss1, kiss2, kissr1, and kissr2 (166)] system genes all generate zebrafish with normal gametogenesis, suggesting that this species may have a high compensatory mechanism [for reviews (167,168)] and may not reflect the situation observed in all teleosts.…”