Investigating the role of prostaglandin receptor isoform EP4b in zebrafish ovulation

•Zebrafish ovarian follicles express multiple prostaglandin receptor subtypes.•Only the expression of receptor subtype EP4b increased during spontaneous ovulation.•Treatment with Ovaprim to induce ovulation increased expression of EP4b.•In vitro treatment of full-grown follicles with 17,20βP increased EP4b expression.•EP4 receptor antagonists block the effect of Ovaprim but not EP1 or EP2 antagonists. Prostaglandins (PGs) are a class of fatty acid-derived hormones that play an essential role in the regulation of ovulation of teleosts. This study investigated the various isoforms of ovarian PG receptors in the zebrafish ovary and their role in ovulation. Using real time qPCR, six PG receptor isoforms (ptger1a, ptger1b, ptger2a, ptger4a, ptger4b, and ptgfr) were shown to be expressed in the ovary. Only the PG receptor isoform ptger4b was upregulated at the time of ovulation in vivo, or following treatment in vivo with Ovaprim, which contains a gonadotropin releasing hormone analogue and a dopamine receptor antagonist and stimulates ovulation. Treatment of full-grown follicles with the maturation-inducing hormone 17α,20β-dihydroxy-4-pregnen-3-one (17,20βP) in vitro also induced expression of EP4b mRNA. Females ovulate in vivo after injection with Ovaprim, or injection with Ovaprim and inhibitors of EP1 (ONO-8130) or EP2 (TG4-155) function; they do not ovulate when injected with Ovaprim and an EP4 inhibitor (GW237368x). These findings suggest that the EP4 receptor, in particular the EP4b isoform, is essential for ovulation.