Finasteride interferes with prostaglandin-induced CatSper signalling in human sperm

Area of Science:

• Reproductive Biology
• Endocrinology
• Sperm Physiology

Background:

• Calcium (Ca2+) signaling is crucial for human sperm functions essential for fertilization.
• Endocrine-disrupting chemicals can activate the CatSper Ca2+ channel, disrupting sperm Ca2+ signaling.
• Finasteride, used for hair loss, is structurally similar to progesterone and has been linked to male infertility.

Purpose of the Study:

• To investigate if finasteride affects human sperm calcium (Ca2+) signaling in a manner similar to progestogens.
• To assess the impact of finasteride on CatSper-mediated Ca2+ signaling, sperm penetration, and acrosome reaction.

Main Methods:

• Human sperm were analyzed in cell suspensions using single-cell imaging to monitor intracellular Ca2+ concentration ([Ca2+]i).
• Sperm penetration into a viscous medium and acrosome reaction were assessed.
• The effects of finasteride on Ca2+ signaling induced by progesterone and prostaglandin E1 (PGE1) were evaluated.

Main Results:

• Finasteride induced a minor, transient increase in [Ca2+]i at physiological concentrations.
• Finasteride inhibited PGE1-induced Ca2+ signals, indicating mixed-type inhibition.
• No significant effects of finasteride were observed on progesterone-induced Ca2+ signaling, acrosome reaction, or sperm viability.
• Finasteride reduced PGE1-induced sperm penetration at concentrations exceeding those typically found in blood and seminal fluids.

Conclusions:

• Finasteride may influence human sperm Ca2+ signaling by interacting with the PGE1-binding site.
• The clinical significance of finasteride's effect on fertilization requires further investigation.
• Potential side effects related to prostaglandin signaling interference by finasteride in other bodily systems warrant further study.