Finasteride interferes with prostaglandin-induced CatSper signalling in human sperm

Ca2+ signalling controls human sperm functions necessary for successful fertilization. Multiple endocrine-disrupting chemicals have been found to activate the CatSper Ca2+ channel and thereby interfering with Ca2+ signalling in human sperm. Finasteride is prescribed to men in the fertile age to treat hair loss and its use has been associated with impaired male fertility. Due to the structural relatedness of finasteride to the endogenous CatSper ligand progesterone, this study aimed to investigate whether finasteride affects human sperm in a progestogen-like manner. The effect of finasteride on Ca2+ signalling via CatSper in human sperm was investigated in cell suspensions by single-cell imaging. Additionally, effects on sperm penetration into viscous medium and acrosome reaction were assessed. Finasteride alone caused a minor transient rise in the intracellular, free Ca2+ concentration ([Ca2+](i)) at physiologically relevant concentrations. Ca2+ signals induced by PGE(1) were inhibited by finasteride displaying mixed type of inhibition consistent with multiple binding sites. Finasteride did not interfere with progesterone-induced Ca2+ signalling and no effect on acrosome reaction or sperm viability was found. Finasteride significantly decreased PGE(1)-induced penetration into viscous medium but in concentrations above what is measured in blood and seminal fluids during regular finasteride administration. In conclusion, the use of finasteride may affect Ca2+ signalling in human sperm through an interaction with the PGE(1)-binding site, but to which extend it alters the chances of a successful fertilization needs further investigation. It remains to be investigated whether finasteride administration may give rise to side effects by interfering with prostaglandin signalling elsewhere in the human body.

Automated summary

Finasteride caused a minor transient rise in intracellular Ca2+ concentration in human sperm, potentially affecting Ca2+ signalling through interaction with the PGE(1)-binding site. It did not interfere with progesterone-induced Ca2+ signalling, acrosome reaction, or sperm viability. Finasteride decreased PGE(1)-induced penetration into viscous medium at concentrations higher than those typically found in blood or seminal fluids. Further investigation is needed to determine the extent to which finasteride may impact successful fertilization and potential side effects on prostaglandin signalling in other parts of the human body.