The role and regulation of prostaglandins and their receptors in ovulation in the zebrafish, Danio rerio




Baker, Sheridan

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University of Guelph


Prostaglandins (PGs) are fatty-acid derived hormones implicated in ovulation, but their exact role is poorly understood. This thesis investigated how prostaglandins and their receptors are involved in regulating ovulation in zebrafish. A combination of in vitro, in vivo, and in silico methods were used to examine the roles of various prostaglandin receptors, the regulation of downstream genes by prostaglandins, and the regulation of prostaglandins and their receptors by the progestin 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P). Using real time quantitative PCR, six PG receptor isoforms were identified in the zebrafish ovary. The isoform ptger4b was upregulated around the time of ovulation in vivo or following treatment in vivo with Ovaprim, a potent stimulator of ovulation, or in vitro in full-grown follicles treated with 17,20β-P. An inhibitor of EP4 function blocked the actions of Ovaprim on ovulation. This suggests that the EP4 receptor, in particular the EP4b isoform, is essential for ovulation. When examining the downstream targets of PGs, four members of the A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) family (ADAMTS1, ADAMTS5, ADAMTS9, ADAMTS16), which are implicated in follicular rupture, were identified in the ovary. Treatment with PGE2, but not PGF2α, led to upregulation of only adamts1 in vitro in full-grown follicles and this effect was blocked by the EP4 inhibitor. These findings suggest that adamts1 is regulated by PGE2 via the EP4 series receptor. In other studies, the nuclear progesterone receptor (Pgr) had the highest expression in full-grown and mature follicles compared to earlier growth stages. In silico analysis of selected genes showed that ptger4a and ptger4b contain a PRE in their promoter regions and in vitro studies revealed that ptger4b was upregulated in response to 17,20β-P. Additionally, expression of both PLA2G4A mRNA and protein, a key enzyme in prostaglandin synthesis, was upregulated in response to treatment with 17,20β-P. Together, these results demonstrate the importance of Pgr in ovulation due to its involvement in prostaglandin production by regulating PLA2G4A and function by controlling expression of the EP4b receptor. Collectively, the results of this thesis establish PGE2 and its EP4b receptor as critical molecules in regulating ovulation in zebrafish.



Zebrafish, Ovulation, Prostaglandin, Progestin, ADAMTS1, Regulation, 17,20BP, PGE2


Baker, S.J.C., Van Der Kraak, G., 2019. Investigating the role of prostaglandin receptor isoform EP4b in zebrafish ovulation. Gen. Comp. Endocrinol. 283, 113228.