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

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.

Authors+Show Affiliations

Department of Biology, East Carolina University , Greenville, NC , USA ; College of Ocean and Earth Sciences, Xiamen University , Xiamen , China.Department of Biology, East Carolina University , Greenville, NC , USA ; College of Ocean and Earth Sciences, Xiamen University , Xiamen , China ; State Key Laboratory of Marine Environmental Science, Xiamen University , Xiamen , China.Department of Biology, East Carolina University , Greenville, NC , USA.College of Ocean and Earth Sciences, Xiamen University , Xiamen , China ; State Key Laboratory of Marine Environmental Science, Xiamen University , Xiamen , China.College of Ocean and Earth Sciences, Xiamen University , Xiamen , China ; State Key Laboratory of Marine Environmental Science, Xiamen University , Xiamen , China.Department of Biology, East Carolina University , Greenville, NC , USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25852646

Citation

Zhu, Yong, et al. "Nuclear Progestin Receptor (pgr) Knockouts in Zebrafish Demonstrate Role for Pgr in Ovulation but Not in Rapid Non-genomic Steroid Mediated Meiosis Resumption." Frontiers in Endocrinology, vol. 6, 2015, p. 37.
Zhu Y, Liu D, Shaner ZC, et al. Nuclear progestin receptor (pgr) knockouts in zebrafish demonstrate role for pgr in ovulation but not in rapid non-genomic steroid mediated meiosis resumption. Front Endocrinol (Lausanne). 2015;6:37.
Zhu, Y., Liu, D., Shaner, Z. C., Chen, S., Hong, W., & Stellwag, E. J. (2015). Nuclear progestin receptor (pgr) knockouts in zebrafish demonstrate role for pgr in ovulation but not in rapid non-genomic steroid mediated meiosis resumption. Frontiers in Endocrinology, 6, p. 37. doi:10.3389/fendo.2015.00037.
Zhu Y, et al. Nuclear Progestin Receptor (pgr) Knockouts in Zebrafish Demonstrate Role for Pgr in Ovulation but Not in Rapid Non-genomic Steroid Mediated Meiosis Resumption. Front Endocrinol (Lausanne). 2015;6:37. PubMed PMID: 25852646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nuclear progestin receptor (pgr) knockouts in zebrafish demonstrate role for pgr in ovulation but not in rapid non-genomic steroid mediated meiosis resumption. AU - Zhu,Yong, AU - Liu,Dongteng, AU - Shaner,Zoe C, AU - Chen,Shixi, AU - Hong,Wanshu, AU - Stellwag,Edmund J, Y1 - 2015/03/19/ PY - 2015/02/05/received PY - 2015/03/06/accepted PY - 2015/4/9/entrez PY - 2015/4/9/pubmed PY - 2015/4/9/medline KW - TALENs KW - final oocyte maturation KW - gene editing KW - knockout KW - meiosis resumption KW - non-genomic progestin signaling KW - ovulation KW - progestin receptor SP - 37 EP - 37 JF - Frontiers in endocrinology JO - Front Endocrinol (Lausanne) VL - 6 N2 - 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. SN - 1664-2392 UR - https://www.unboundmedicine.com/medline/citation/25852646/Nuclear_progestin_receptor__pgr__knockouts_in_zebrafish_demonstrate_role_for_pgr_in_ovulation_but_not_in_rapid_non_genomic_steroid_mediated_meiosis_resumption_ L2 - https://dx.doi.org/10.3389/fendo.2015.00037 DB - PRIME DP - Unbound Medicine ER -