PPARβ/δ Ligands Regulate Oxidative Status and Inflammatory Response in Inflamed Corpus Luteum-An In Vitro Study

by Selleckchem | Jul 12 2023

Inflammation in the female reproductive system causes serious health problems including infertility. The aim of this study was to determine the in vitro effects of peroxisome proliferator-activated receptor-beta/delta (PPARβ/δ) ligands on the transcriptomic profile of the lipopolysaccharide (LPS)-stimulated pig corpus luteum (CL) in the mid-luteal phase of the estrous cycle using RNA-seq technology. The CL slices were incubated in the presence of LPS or in combination with LPS and the PPARβ/δ agonist-GW0724 (1 μmol/L or 10 μmol/L) or the antagonist-GSK3787 (25 μmol/L). We identified 117 differentially expressed genes after treatment with LPS; 102 and 97 differentially expressed genes after treatment, respectively, with the PPARβ/δ agonist at a concentration of 1 μmol/L or 10 μmol/L, as well as 88 after the treatment with the PPARβ/δ antagonist. In addition, biochemical analyses of oxidative status were performed (total antioxidant capacity and activity of peroxidase, catalase, superoxide dismutase, and glutathione S-transferase). This study revealed that PPARβ/δ agonists regulate genes involved in the inflammatory response in a dose-dependent manner. The results indicate that the lower dose of GW0724 showed an anti-inflammatory character, while the higher dose seems to be pro-inflammatory. We propose that GW0724 should be considered for further research to alleviate chronic inflammation (at the lower dose) or to support the natural immune response against pathogens (at the higher dose) in the inflamed corpus luteum.

Comments:

The study aimed to investigate the effects of peroxisome proliferator-activated receptor-beta/delta (PPARβ/δ) ligands on the gene expression profile of the pig corpus luteum (CL) during the mid-luteal phase of the estrous cycle. Inflammation in the female reproductive system, particularly in the CL, can lead to serious health issues such as infertility. The researchers utilized RNA-seq technology to analyze the transcriptomic changes induced by lipopolysaccharide (LPS), a known inducer of inflammation, in combination with PPARβ/δ agonist (GW0724) or antagonist (GSK3787) at different concentrations.

The experiment involved incubating CL slices with LPS alone or in combination with either GW0724 (at concentrations of 1 μmol/L or 10 μmol/L) or GSK3787 (at a concentration of 25 μmol/L). Afterward, the researchers examined the gene expression profiles using RNA-seq and identified 117 differentially expressed genes in response to LPS treatment. Furthermore, they observed 102 and 97 differentially expressed genes when treated with the lower and higher concentration of the PPARβ/δ agonist, respectively. The treatment with the PPARβ/δ antagonist resulted in 88 differentially expressed genes.

To complement the gene expression analysis, the researchers also conducted biochemical analyses to evaluate the oxidative status of the CL. They measured the total antioxidant capacity and the activity of enzymes involved in antioxidant defense, including peroxidase, catalase, superoxide dismutase, and glutathione S-transferase.

The study findings demonstrated that PPARβ/δ agonists regulate genes associated with the inflammatory response in a dose-dependent manner. The lower concentration of GW0724 exhibited an anti-inflammatory effect, while the higher concentration seemed to promote inflammation. These results suggest that GW0724 could be further investigated for its potential to alleviate chronic inflammation at lower doses or enhance the natural immune response against pathogens at higher doses in inflamed corpus luteum.

In conclusion, this study highlights the role of PPARβ/δ agonists in modulating the inflammatory response within the corpus luteum. By elucidating the specific gene expression changes and their dose-dependent nature, the research provides insights into the potential therapeutic applications of GW0724 in managing inflammation in the female reproductive system. Further research is warranted to explore the clinical implications of these findings and validate the effects of PPARβ/δ ligands on reproductive health.