Related Experiment Video
Updated: Nov 3, 2025
A Modified Co-Culture System for Understanding Granulosa-Theca Cell Interactions in the Bovine Ovary
Published on: September 19, 2025
Death Processes in Bovine Theca and Granulosa Cells Modelled and Analysed Using a Systems Biology Approach
Malgorzata J McEvoy1,2, Emilia Sinderewicz3, Leo Creedon1
1Mathematical Modelling Research Group, Institute of Technology Sligo, Ash Lane, Sligo, F91 YW50 Sligo, Ireland.
Abstract:
In this paper, newly discovered mechanisms of atresia and cell death processes in bovine ovarian follicles are investigated. For this purpose the mRNA expression of receptor interacting protein kinases 1 and 3 (RIPK1 and RIPK3) of the granulosa and theca cells derived from healthy and atretic follicles are studied. The follicles were assigned as either healthy or atretic based on the estradiol to progesterone ratio. A statistically significant difference was recorded for the mRNA expression of a RIPK1 and RIPK3 between granulosa cells from healthy and atretic follicles. To further investigate this result a systems biology approach was used. The genes playing roles in necroptosis, apoptosis and atresia were chosen and a network was created based on human genes annotated by the IMEx database in Cytoscape to identify hubs and bottle-necks. Moreover, correlation networks were built in the Cluepedia plug-in. The networks were created separately for terms describing apoptosis and programmed cell death. We demonstrate that necroptosis (RIPK-dependent cell death pathway) is an alternative mechanism responsible for death of bovine granulosa and theca cells. We conclude that both apoptosis and necroptosis occur in the granulosa cells of dominant follicles undergoing luteinisation and in the theca cells from newly selected follicles.
Insights
This study reveals necroptosis, a programmed cell death pathway, as a key mechanism in bovine ovarian follicle atresia. Researchers investigated receptor interacting protein kinases (RIPK1 and RIPK3) in healthy and atretic follicles.
Area of Science:
- Reproductive biology
- Cellular and molecular biology
- Veterinary science
Background:
- Ovarian follicle atresia is a crucial process in female reproduction.
- Understanding the molecular mechanisms of cell death in follicles is essential for reproductive health.
Purpose of the Study:
- To investigate novel mechanisms of atresia and cell death in bovine ovarian follicles.
- To examine the role of receptor interacting protein kinases (RIPK1 and RIPK3) in follicle cell death.
Main Methods:
- mRNA expression analysis of RIPK1 and RIPK3 in granulosa and theca cells from healthy and atretic bovine follicles.
- Follicle classification based on estradiol to progesterone ratio.
- Systems biology approach using network analysis (Cytoscape, Cluepedia) of genes involved in apoptosis, necroptosis, and atresia.
Main Results:
- Statistically significant differences in RIPK1 and RIPK3 mRNA expression were observed between healthy and atretic follicle granulosa cells.
- Network analysis identified key genes and pathways involved in programmed cell death.
- Necroptosis, a RIPK-dependent cell death pathway, was identified as an alternative mechanism for bovine granulosa and theca cell death.
Conclusions:
- Both apoptosis and necroptosis are active processes in bovine ovarian follicles.
- Necroptosis contributes to cell death in granulosa cells of dominant follicles during luteinisation and in theca cells of newly selected follicles.
