Effects of ulipristal acetate on sperm DNA fragmentation during in vitro incubation

Abstract

Objective Ulipristal acetate (UPA) acts as an emergency contraceptive by inhibiting ovulation. This study explores possible additional effects on the fragmentation of sperm DNA during in vitro incubation.

Methods Motile spermatozoa from healthy donors were selected by swim-up and incubated under capacitating conditions in control medium or with UPA (1, 10, 100, 1,000 or 10,000 ng/ml). In some experiments, 200 μM of H₂O₂ were added to induce oxidative stress. The sperm chromatin dispersion test was performed to analyse DNA integrity (400 cells; 1000×). Lipid peroxidation (thiobarbituric acid assay), induced-acrosome reaction (AR) and sperm vitality (Eosin Y) were also evaluated in spermatozoa exposed to UPA and/or H₂O₂.

Results During sperm incubation, the percentage of fragmented DNA increased significantly, from 15.0 ± 1.3 to 41.0 ± 4.5% (p < 0.001). In the presence of UPA, DNA fragmentation decreased significantly (p < 0.05), in a dose-dependent manner. At 100 and 1000 ng/ml, UPA also counteracted the effect of H₂O₂ and prevented DNA fragmentation. No effect on sperm vitality, lipid peroxidation or induced-AR was found with any treatment.

Conclusions During in vitro sperm capacitation DNA fragmentation increased but the latter was counteracted in the presence of UPA, which possibly acted as a scavenger of reactive oxygen species produced by spermatozoa.

Keywords:

• Spermatozoa
• Ulipristal acetate
• Sperm chromatin dispersion test
• DNA fragmentation

ACKNOWLEDGEMENTS

The authors are indebted to Dr Régine Sitruk- Ware of the Population Council, New York and to Dr Delphine Levy of HRA Pharma, Paris, France for the kind donation of ulipristal acetate.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and the writing of the text. The study received partial funding (grant 573747/2008-3) from the Brazilian National Research Council (CNPq).