Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Defining the role of Glucocorticoid signalling in the mouse ovary (#479)

Imogen Abbott 1 2 , Jacinta H Martin 1 2 , Shanu Parameswaran 1 2 , Liza O'Donnell 3 , Natalie Reed 1 , Sarah Smith 1 , Diane Rebourcet 1 , Lee Smith 3 , Anne-Louise Gannon 1 2
  1. School of Environmental and Life Sciences, The University of Newcastle, Newcastle, NSW, Australia
  2. Infertility and Reproduction Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia
  3. Griffith University, Southport, QLD, Australia

Glucocorticoids are produced in the adrenal gland and act via glucocorticoid receptors (GR, encoded by Nr3c1). They are essential to regulate numerous physiological processes, including glucose metabolism, inflammation, stress response, growth/development, and the reproductive system. In the ovary, glucocorticoids have been shown to impact the oocyte and the cumulus, granulosa and luteal cells. Knowledge surrounding the role of glucocorticoid signalling in theca cells, the primary endocrine unit of the ovary, however, is critically lacking. This study aimed to define the role(s) of glucocorticoid signalling in the ovary by investigating the effects of genetic ablation of GR expression from the theca cells in the mouse ovary. We used a cre-loxp system to generate GR theca-cell-specific knockout mice (GRLTKO) by breeding Nr3c1 floxed mice with Cyp17- iCre promotor mice, resulting in the deletion of Nr3c1 in theca cells. Histology analysis and follicle counts were conducted on 14-week-old mouse ovaries to assess ovarian health. Immunofluorescence and RT-qPCR for steroidogenic enzymes, receptors and key functional markers were used to assess Cre efficacy and the effect of GR ablation on steroidogenesis. Analyses revealed only partial ablation of GR in GRLTKO mice theca cells. Despite this, the ovaries of these mice exhibited ovarian disruption, such that there was a significant increase in the number of secondary and tertiary follicles undergoing atresia. These follicles were characterised by increased presence of pyknotic nuclei, granulosa cell disorganisation and the oocyte within the follicle appeared to have prematurely undergone meiotic maturation. This disruption occurred without altering the expression of steroidogenic enzymes or any overt changes in overall follicle number. These observations highlight the importance of GR signalling in theca cells and its previously unappreciated role in maintaining complex signalling pathways required for the appropriate timing of meiosis resumption in the oocyte.