Effects of peroxisome proliferator-activated receptor γ activation on human sperm functions

Abstract

OBJECTIVE: Peroxisome Proliferation-Activated Receptor γ (PPARγ) regulates cellular energy usage. Previous reports showed human and mouse oviducts produce PGD2. Its derivative, 15δ-PGJ2, is a PPARγ ligand. A recent report showed human sperms expresses PPARγ and that its activation by synthetic ligand (troglitazone) enhances sperm capacitation, acrosome reaction, and overall motility. It is not clear which parameter(s) is enhanced by PPARγ ligand and the extent of enhancement in sperms with low motility.DESIGN: Observational study.MATERIALS AND METHODS: Samples for routine semen analyses were used. Using 20 millions/ml and 50% motility as cutoffs, they were divided into: normal concentration/motility, low concentration/low motility, normal concentration/low motility. A Hamilton-Thorne semen analyzer was used to determine motility, track speed, amplitude of lateral head movement. Hyper-activated sperms were defined as those displaying curvilinear velocity of >100 μm/sec and linearity of <50%. The acrosome reaction was determined based on triple stain technique. Troglitazone (1 μM) was used; observations were made every 30 min for 120 min. Mix model analyses were used to analyze the data. A p< 0.05 was considered as significant.RESULTS: Ten samples from each group were analyzed. There was no significant difference in all kinetic parameters studied including those showing hyper-activation movement. However, the capacitation/acrosome reaction was significantly enhanced by troglitazone (p<0.005). It was most significant in normal concentration/motility group (p< 0.001), marginally significant in the low concentration/motility group (p=0.059), and not significant in normal concentration/low motility group.CONCLUSIONS: PPARγ activation enhances the capacitation/acrosome reaction of normal sperm samples but not others. Oviductal PGD2 may, via PPARγ, enhance sperm capacitation/acrosome reaction in a natural setting. Thus, synthetic PPARγ ligand may be used to enhance sperm function in ART. OBJECTIVE: Peroxisome Proliferation-Activated Receptor γ (PPARγ) regulates cellular energy usage. Previous reports showed human and mouse oviducts produce PGD2. Its derivative, 15δ-PGJ2, is a PPARγ ligand. A recent report showed human sperms expresses PPARγ and that its activation by synthetic ligand (troglitazone) enhances sperm capacitation, acrosome reaction, and overall motility. It is not clear which parameter(s) is enhanced by PPARγ ligand and the extent of enhancement in sperms with low motility. DESIGN: Observational study. MATERIALS AND METHODS: Samples for routine semen analyses were used. Using 20 millions/ml and 50% motility as cutoffs, they were divided into: normal concentration/motility, low concentration/low motility, normal concentration/low motility. A Hamilton-Thorne semen analyzer was used to determine motility, track speed, amplitude of lateral head movement. Hyper-activated sperms were defined as those displaying curvilinear velocity of >100 μm/sec and linearity of <50%. The acrosome reaction was determined based on triple stain technique. Troglitazone (1 μM) was used; observations were made every 30 min for 120 min. Mix model analyses were used to analyze the data. A p< 0.05 was considered as significant. RESULTS: Ten samples from each group were analyzed. There was no significant difference in all kinetic parameters studied including those showing hyper-activation movement. However, the capacitation/acrosome reaction was significantly enhanced by troglitazone (p<0.005). It was most significant in normal concentration/motility group (p< 0.001), marginally significant in the low concentration/motility group (p=0.059), and not significant in normal concentration/low motility group. CONCLUSIONS: PPARγ activation enhances the capacitation/acrosome reaction of normal sperm samples but not others. Oviductal PGD2 may, via PPARγ, enhance sperm capacitation/acrosome reaction in a natural setting. Thus, synthetic PPARγ ligand may be used to enhance sperm function in ART.