Related Experiment Video
Updated: Jul 15, 2026
A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome
Published on: October 2, 2018
Impaired progesterone production in Nr5a2+/- mice leads to a reduction in female reproductive function
Cassandre Labelle-Dumais1, Jean-François Paré, Luc Bélanger
1Division of Experimental Medicine, Department of Obstetrics and Gynecology, McGill University, RVH, Montreal, Québec, Canada H3A 1A1.
Abstract:
NR5A2 is an orphan nuclear receptor involved in cholesterol metabolism and embryogenesis. The high level of expression of NR5A2 in the ovary and its involvement in the regulation of steroidogenic gene expression also suggest a role for this transcription factor in female reproductive function. In vivo evidence for a role for NR5A2 in fertility, however, is still lacking. In order to address this possibility, we used Nr5a2+/- mice to demonstrate that heterozygosity for a null mutation of Nr5a2 leads to a decreased fertility in females. Our results indicate that although Nr5a2+/- mice display normal follicular development, ovulation, and estrogen production, they exhibit altered luteal function. More specifically, we show that the reduced reproductive ability of Nr5a2+/- females arises from a reduction in circulating progesterone concentrations and can be rescued by exogenous progesterone supplementation. This study therefore provides the first in vivo evidence for a role of NR5A2 in reproductive function and steroidogenesis.
Insights
The nuclear receptor NR5A2 (Nuclear Receptor subfamily 5, group A, member 2) is crucial for female fertility. Reduced NR5A2 levels in mice impaired reproductive function by altering progesterone production, highlighting its role in female reproduction and steroidogenesis.
Area of Science:
- Reproductive biology
- Endocrinology
- Molecular genetics
Background:
- Nuclear Receptor subfamily 5, group A, member 2 (NR5A2) is implicated in cholesterol metabolism and embryogenesis.
- High NR5A2 expression in ovaries suggests a role in female reproductive function and steroidogenic gene regulation.
- In vivo evidence for NR5A2's role in female fertility was previously lacking.
Purpose of the Study:
- To investigate the in vivo role of NR5A2 in female reproductive function and fertility.
- To determine the specific mechanisms underlying NR5A2's influence on fertility.
Main Methods:
- Utilized heterozygous knockout mice (Nr5a2+/-) to study the effects of reduced NR5A2 levels.
- Assessed follicular development, ovulation, estrogen production, and luteal function in Nr5a2+/- female mice.
- Measured circulating progesterone concentrations and evaluated the effects of progesterone supplementation.
Main Results:
- Nr5a2+/- female mice exhibited decreased fertility.
- Follicular development, ovulation, and estrogen production remained normal in heterozygous mice.
- Altered luteal function was observed, characterized by reduced circulating progesterone concentrations.
- Exogenous progesterone supplementation rescued the reduced reproductive ability in Nr5a2+/- females.
Conclusions:
- This study provides the first in vivo evidence for NR5A2's essential role in female reproductive function.
- NR5A2 is critical for maintaining adequate progesterone levels during the luteal phase, impacting fertility.
- NR5A2 acts as a key regulator of steroidogenesis in the female reproductive system.
