Nuclear progestin receptor (Pgr) knockouts in zebrafish demonstrate role for Pgr in ovulation but not in rapid non-genomic steroid mediated meiosis resumption
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Date
2015
Authors
Zhu, Yong
Liu, Dongteng
Shaner, Zoe C.
Chen, Shixi
Hong, Wanshu
Stellwag, Edmund J.
Journal Title
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Abstract
Progestins, progesterone derivatives, are the most critical signaling steroid for initiating final
oocyte maturation (FOM) and ovulation, in order to advance fully-grown immature oocytes
to become fertilizable eggs in basal vertebrates. It is well-established that progestin induces
FOM at least partly through a membrane receptor and a non-genomic steroid signaling
process, which precedes progestin triggered ovulation that is mediated through a nuclear
progestin receptor (Pgr) and genomic signaling pathway.To determine whether Pgr plays a
role in a non-genomic signaling mechanism during FOM, we knocked out Pgr in zebrafish
using transcription activator-like effector nucleases (TALENs) and studied the oocyte maturation phenotypes of Pgr knockouts (Pgr-KOs). Three TALENs-induced mutant lines with
different frame shift mutations were generated. Homozygous Pgr-KO female fish were
all infertile while no fertility effects were evident in homozygous Pgr-KO males. Oocytes
developed and underwent FOM normally in vivo in homozygous Pgr-KO female compared
to the wild-type controls, but these mature oocytes were trapped within the follicular cells
and 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 with
human chronic gonadotropin (HCG) or progestin (17α,20β-dihydroxyprogesterone or DHP),
which typically induce FOM and ovulation in wild-type oocytes. The results indicate that
anovulation and infertility in homozygous Pgr-KO female fish was, at least in part, due to a
lack of functional Pgr-mediated genomic progestin signaling in the follicular cells adjacent
to the oocytes. Our study of Pgr-KO supports previous results that demonstrate a role for
Pgr in steroid-dependent genomic signaling pathways leading to ovulation, and the first
convincing evidence that Pgr is not essential for initiating non-genomic progestin signaling
and triggering of meiosis resumption.