Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/135198
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Intraovarian, Isoform-Specific Transcriptional Roles of Progesterone Receptor in Ovulation |
Author: | Smith, K.M. Dinh, D.T. Akison, L.K. Nicholls, M. Dunning, K.R. Morimoto, A. Lydon, J.P. Russell, D.L. Robker, R.L. |
Citation: | Cells, 2022; 11(9):1-23 |
Publisher: | MDPI AG |
Issue Date: | 2022 |
ISSN: | 2073-4409 2073-4409 |
Statement of Responsibility: | Kirsten M. Smith, Doan T. Dinh, Lisa K. Akison, Matilda Nicholls, Kylie R. Dunning, Atsushi Morimoto, John P. Lydon, Darryl L. Russell, and Rebecca L. Robker |
Abstract: | Progesterone receptor (PGR) activity is obligatory for mammalian ovulation; however, there is no established direct functional pathway explaining how progesterone receptor completely and specifically regulates oocyte release. This study examined the overarching cell- and isoform-specific effects of the PGR within each cellular compartment of the ovary, using mice null for the PGR (PRKO), as well as isoform-specific null mice. The PGR was expressed in ovarian granulosa and stromal cells and although PRKO ovaries showed no visible histological changes in preovulatory ovarian morphology, follicle rupture did not occur. Reciprocal ovarian transplant experiments established the necessity of ovarian PGR expression for ovulation. Cumulus–oocyte complexes of PRKO mice exhibited normal morphology but showed some altered gene expression. The examination of mitochondrial activity showed subtle differences in PRKO oocytes but no differences in granulosa cell respiration, glycolysis or beta-oxidation. Concurrently, RNA-seq identified novel functional pathways through which the PGR may regulate ovulation. PGR-A was the predominant transcriptionally active isoform in granulosa cells and 154 key PGR-dependent genes were identified, including a secondary network of transcription factors. In addition, the PGR regulated unique gene networks in the ovarian stroma. Collectively, we establish the effector pathways activated by the PGR across the ovarian cell types and conclude that PGR coordinates gene expression in the cumulus, granulosa and stromal cells at ovulation. Identifying these networks linking the PGR to ovulation provides novel targets for fertility therapeutics and nonhormonal contraceptive development. |
Keywords: | progesterone receptor PGR-A PGR-B PRKO transcriptome ovulation ovarian stroma granulosa cells pathways analysis respiration |
Rights: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). |
DOI: | 10.3390/cells11091563 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1011297 http://purl.org/au-research/grants/nhmrc/1130364 |
Published version: | http://dx.doi.org/10.3390/cells11091563 |
Appears in Collections: | Obstetrics and Gynaecology publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_135198.pdf Restricted Access | Published version | 4.34 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.