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

Abstract

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.

Keywords: F2-isoprostanes; PPARγ expression; human spermatozoa; normozoospermia; resolvin D1; urogenital infections; varicocele.

Figure 1

Box plots representing the sperm morphology % (A), the sperm vitality % (B), the seminal F₂-IsoPs pg/mL(C), the seminal RvD1 pg/mL (D), and sperm PPARγ relative expression (E) in the three analyzed groups. N = donors with normal parameters with negative anamnesis and clinical investigation; N + UI = donors with normal parameters and urogenital infections; N + V = donors with normal parameters and varicocele. * p < 0.05, ** p < 0.01, *** p < 0.001.