# PPARγ Expression in Human Spermatozoa and Its Relationship with Seminal F2-Isoprostanes and Resolvin D1 in the Presence of Varicocele and Urogenital Infections

## TL;DR

This study shows that PPARγ expression in sperm is reduced in men with varicocele or urogenital infections, which are linked to higher oxidative stress and inflammation.

## Contribution

The study reveals a novel link between PPARγ expression in sperm and oxidative stress/inflammation in male infertility conditions.

## Key findings

- PPARγ expression is reduced in men with varicocele or urogenital infections.
- Elevated F2-IsoPs and RvD1 levels are observed in these conditions.
- PPARγ correlates with sperm morphology and vitality, suggesting a role in sperm health.

## Abstract

One of the most important knowledge acquisitions in the field of male infertility involves the relevant role of oxidative stress that, together with inflammation, is a common finding in many reproductive pathologies as varicocele, urogenital infections. Here, we studied the impact of these pathologies on sperm PPARγ, a transcription factor activated by polyunsaturated fatty acids and fatty acid derivatives and a regulating agent in antioxidant response. PPARγ causes a decrease in the production of proinflammatory cytokines, and it therefore has a significant involvement in controlling inflammation. Considering oxidative stress and inflammatory status, F2-IsoPs, prostaglandin-like products derived from arachidonic acid, and RvD1, a resolvin acting as lipid mediator of resolution of inflammation, were measured. The main results obtained in this study indicate a reduced PPARγ expression and high levels of F2-IsoPs and RvD1 in cases with varicocele and urogenital infections. Therefore, the reduced expression of PPARγ in human ejaculated spermatozoa is influenced by seminal oxidative stress and inflammation. PPARγ could be potentially modulated by its natural or artificial ligand, affording new therapeutic opportunities for a potential treatment for male infertility, increasing the performance of spermatozoa.

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) is a regulating agent in antioxidant response also involved in controlling inflammation. The impact of varicocele and urogenital infections on sperm PPARγ expression was studied. The PPARγ gene expression was investigated in spermatozoa of 26 normozoospermic men grouped according to their clinical conditions: normal semen parameters (N), normal semen parameters and varicocele (N + V), and normal semen parameters and urogenital infections (N + UI). Sperm PPARγ expression was correlated with F2-isoprostanes (F2-IsoPs), as markers of lipid peroxidation, and Resolvin D1 (RvD1), a pro-resolving mediator in inflammation. Sperm PPARγ expression was evaluated through comparative real-time PCR, and F2-IsoPs and RvD1 were quantified in the seminal plasma via GC/NCI-MS/MS and immunoassay, respectively. PPARγ expression correlates positively with sperm morphology and vitality and negatively with F2-IsoPs and RvD1. Sperm morphology positively correlates with vitality and negatively with F2-IsoP and RvD1 levels. Despite the normozoospermia in the three examined groups, sperm morphology and PPARγ expression were significantly reduced in N + V and N + UI groups compared to the N group. Additionally, F2-IsoP and RvD1 levels were elevated in N + V and N + UI patients. These data suggest that PPARγ expression is compromised by inflammation and lipoperoxidation, providing new insights to further explore new possibilities of targeted treatment of male infertility.