Releasing prophase arrest in zebrafish oocyte: synergism between maturational steroid and Igf1

Abstract

Binding of 17b-estradiol (E 2 ) to novel G-protein coupled receptor, Gper1, promotes intra-oocyte adenylyl cyclase activity and transactivates epidermal growth factor receptor to ensure prophase-I arrest. Although involvement of either membrane progestin receptor (mPR) or Igf system has been implicated in regulation of meiosis resumption, possibility of concurrent activation and potential synergism between 17a,20b-dihydroxy-4-pregnen-3-one (DHP)-and Igf-mediated signalling cascades in alleviating E 2 inhibition of oocyte maturation (OM) has not been investigated. Here using zebrafish (Danio rerio) defolliculated oocytes, we examined the effect of DHP and Igf1, either alone or in combination, in presence or absence of E 2 , on OM in vitro. While priming of denuded oocytes with E 2 blocked spontaneous maturation, co-treatment with DHP (3 nM) and Igf1 (10 nM), but not alone, reversed E 2 inhibition and promoted a robust increase in germinal vesicle breakdown (GVBD). Although stimulation with either Igf1 or DHP promoted Akt phosphorylation, pharmacological inhibition of PI3K/Akt signalling prevented Igf1-induced GVBD but delayed DHP action till 4-5 h of incubation. Moreover, high intra-oocyte cAMP attenuates both DHP and Igf1-mediated OM and co-stimulation with DHP and Igf1 could effectively reverse E 2 action on PKA phosphorylation. Interestingly, data from in vivo studies reveal that heightened expression of igf1, igf3 transcripts in intact follicles corresponded well with elevated phosphorylation of Igf1r and Akt, mPRa immunoreactivity, PKA inhibition and accelerated GVBD response just prior to ovulation. This indicates potential synergism between maturational steroid and Igf1 which might have physiological relevance in overcoming E 2 inhibition of meiosis resumption in zebrafish oocytes.

The Expression of Key Guidance Genes at a Forebrain Axon Turning Point Is Maintained by Distinct Fgfr Isoforms but a Common Downstream Signal Transduction Mechanism

“…4 A ). These concentrations were shown previously to be effective in Xenopus and zebrafish in vivo (Westfall et al, 2003; Vergara and Del Rio-Tsonis, 2009; Belgacem and Borodinsky, 2011; Stulberg et al, 2012; Das et al, 2016). In all cases, the control embryos were exposed to the same concentration of DMSO solvent used to dissolve the drugs.…”

Conserved insulin signaling in the regulation of oocyte growth, development, and maturation

“…The role of the insulin‐induced PI3K/AKT signaling pathway in the regulation of oocyte maturation is best characterized in lower vertebrates, owing to the ease of in vitro culture systems, preparation of denuded oocytes divested of follicular cells, and widespread use of cell‐permeable pharmacological agents targeting selective intra‐oocyte kinases and phosphatases (Andersen, Roth, & Conti, ; Chuang et al, ; Das, Pal, & Maitra, ; Mood, Bong, Lee, Ishimura, & Daar, ). In Xenopus , activation of PI3K signaling regulates insulin‐dependent oocyte maturation (Chuang et al, ).…”

Makorin 1 is required for Drosophila oogenesis by regulating insulin/Tor signaling

“…Female reproductive organs rely on the insulin signaling system for proper function and to ensure that oogenesis occurs only when there are enough nutrients available [10]. The insulin signaling pathway and its role in ovarian development is conserved among species [11]. In flies, insulin receptor ( InR ) and insulin substrate protein 1 ( chico ) genetic mutation cause female sterility [12, 13].…”