Das, D., Pal, S., Maitra, S. (2016) Releasing prophase arrest in zebrafish oocyte: Synergism between maturational steroid and Igf1. Reproduction (Cambridge, England). 151(1):59-72.
Binding of estradiol-17β (E2) to novel G-protein coupled receptor, Gper1, promotes intra-oocyte adenylyl cyclase activity and transactivates epidermal growth factor receptor (Egfr) to ensure prophase-I arrest. Although involvement of either membrane progestin receptor (mPR) or insulin-like growth factor (Igf) system has been implicated in regulation of meiosis resumption, possibility of concurrent activation and potential synergism between 17α,20β-dihydroxy-4-pregnen-3-one (DHP)- and Igf-mediated signalling cascades in alleviating E2 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 E2, on OM in vitro. While priming of denuded oocytes with E2 blocked spontaneous maturation, co-treatment with DHP (3 nM) and Igf1 (10 nM), but not alone, reversed E2 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 E2 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 indicating potential synergism between maturational steroid and Igf1 might have physiological relevance in overcoming E2 inhibition of meiosis resumption in zebrafish oocytes.