Effects of pharmacological inhibition of signal transduction pathways in steroid-induced oocyte maturation in rainbow trout

Authors: Weber, Gregory; Radler, Lisa; Birkett, Jill

Submitted to: Aquaculture Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/16/2025
Publication Date: 3/21/2025
Citation: Weber, G.M., Radler, L.M., Birkett, J.E. 2025. Effects of pharmacological inhibition of signal transduction pathways in steroid-induced oocyte maturation in rainbow trout. Aquaculture Reports. 42:Article e102760. https://doi.org/10.1016/j.aqrep.2025.102760.
DOI: https://doi.org/10.1016/j.aqrep.2025.102760

Interpretive Summary: Following the growth phase of the oocyte, changes in the oocyte and its surrounding follicles cells must take place to transform the oocyte into a developmentally competent egg ready for fertilization in a process called ovarian follicle maturation. This process is regulated by an orchestration of hormones and growth factors that signal through multiple signaling pathways in each of the cells involved including the oocyte, that are in part species specific. Understanding this regulation will lead to improved ways to control this process in the hatchery and diagnose why egg quality might be diminished. The two primary regulators of these processes is the steroid maturation inducing hormone (MIH), which is 17,20BP in trout, and the Insulin/Insulin-like growth factor (IGF) family peptides. Understanding how the MIH and the growth factors regulate this process has been complicated by the findings that the MIH and growth factors share signaling pathways. Scientists at NCCCWA have recently shown rainbow trout are unusual in that insulin and IGFs do not regulate ovarian follicle maturation, making the rainbow trout a valuable model to understand regulation by the MIH. The present study identified pathways involved and not involved in MIH control of ovarian follicle maturation in rainbow trout. Even though the growth factors do not regulate ovarian follicle maturation in the rainbow trout, the PI3K pathway, which is thought to be primarily under the regulation of growth factors, is important for MIH induction of follicle maturation in rainbow trout. In addition, results indicate the MEK/MAPK pathway is required for MIH induction of follicle maturation in rainbow trout which is uncommon in lower vertebrates. The findings from this study will aid in the understanding of how hatchery practices affect egg quality and how different modes of reproduction evolve.

Technical Abstract: Gonadotropin, steroids and insulin family growth factors act throughout the follicle-oocyte complex to regulate ovarian follicle maturation. Induction of oocyte maturation by the maturation inducing hormone (MIH) and insulin/insulin-like growth factor (IGF) peptides has received the most attention in lower vertebrates. Receptors for insulin, IGFs, and the MIH are expressed on oocyte membranes although the receptor signaling pathways that activate the maturation promoting factor, which directly induces resumption of meiosis, are species specific and not well characterized in most lower vertebrates. The phosphatidylinositol-3 kinase (Pi3K) pathway, a primary signaling pathway for growth factors, is required not only for growth factor actions, but also for optimal gonadotropin and MIH induction of oocyte maturation in many species. The involvement of the Pi3K pathway in the integration of growth factor and MIH induction of ovarian follicle maturation and oocyte maturation, and why it varies among species, is not well understood. Rainbow trout, (Oncorhynchus mykiss), appear unusual in that insulin and IGFs cannot induce resumption of meiosis or competence of the oocyte to respond to the MIH, 17,20BP making it an interesting species to investigate Pi3K pathway signaling by MIH. In the present study, 17,20BP induction of germinal vesicle breakdown, a marker of resumption of meiosis, and MAPK activation, were blocked or attenuated by pharmacological inhibition of Pi3K (wortmannin, LY294002) or Mek (PD98059, U0126), but were not affected by inhibitors of Akt (ML-9) or mTOR (rapamycin). The results indicate Pi3K and MAPK activation are required for optimal MIH-induction of meiosis resumption in rainbow trout follicles, but Akt and mTOR may be unnecessary.