Nuclear progestin receptor (Pgr) knockouts in zebrafish demonstrate role for Pgr in ovulation but not in rapid non-genomic steroid mediated meiosis resumption

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Yong,Liu,Dongteng,Shaner,Zoe C.,Chen,Shixi,Hong,Wanshu,Stellwag,Edmund J. Zhu (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Progestins, progesterone derivatives, are the most critical signaling steroid for initiating finaloocyte maturation (FOM) and ovulation, in order to advance fully-grown immature oocytesto become fertilizable eggs in basal vertebrates. It is well-established that progestin inducesFOM at least partly through a membrane receptor and a non-genomic steroid signalingprocess, which precedes progestin triggered ovulation that is mediated through a nuclearprogestin receptor (Pgr) and genomic signaling pathway.To determine whether Pgr plays arole in a non-genomic signaling mechanism during FOM, we knocked out Pgr in zebrafishusing transcription activator-like effector nucleases (TALENs) and studied the oocyte maturation phenotypes of Pgr knockouts (Pgr-KOs). Three TALENs-induced mutant lines withdifferent frame shift mutations were generated. Homozygous Pgr-KO female fish wereall infertile while no fertility effects were evident in homozygous Pgr-KO males. Oocytesdeveloped and underwent FOM normally in vivo in homozygous Pgr-KO female comparedto the wild-type controls, but these mature oocytes were trapped within the follicular cellsand failed to ovulate from the ovaries.These oocytes also underwent normal germinal vesicle breakdown (GVBD) and FOM in vitro, but failed to ovulate even after treatment withhuman chronic gonadotropin (HCG) or progestin (17a,20β-dihydroxyprogesterone or DHP),which typically induce FOM and ovulation in wild-type oocytes. The results indicate thatanovulation and infertility in homozygous Pgr-KO female fish was, at least in part, due to alack of functional Pgr-mediated genomic progestin signaling in the follicular cells adjacentto the oocytes. Our study of Pgr-KO supports previous results that demonstrate a role forPgr in steroid-dependent genomic signaling pathways leading to ovulation, and the firstconvincing evidence that Pgr is not essential for initiating non-genomic progestin signalingand triggering of meiosis resumption.

Additional Information

Publication

Other

Language: English

Date: 2015

Keywords

knockout, ovulation, meiosis resumption, final oocyte maturation, non-genomic progestin signaling, TALENs, gene editing, progestin receptor

Email this document to