ß-Elemene Inhibits Human Sperm Function by Affecting Sperm Vitality and Intracellular Calcium.

BACKGROUND/AIMS: ß-Elemene is a bioactive sesquiterpene compound that exhibits a potent anti-tumor effect and is used in various clinical applications. However, little is known about its effect on the male reproductive system. The objective of this study was to investigate the in vitro actions of ß-elemene on human sperm function and elucidate the underlying mechanism. METHODS: The cytotoxicity of ß-elemene toward MCF-10A, MDA-MD-231, and A549 cells was evaluated with cell proliferation and colony formation assays. Additionally, human sperm were treated with different concentrations (0, 10, 20, 40, 80, 160, and 320 µM) of ß-elemene in vitro. The characteristics in human sperm essential for fertilization, including vitality, motility, capacitation, acrosome reaction, responsiveness to progesterone, and intracellular calcium concentration ([Ca2+]i) were examined with a computer-assisted sperm analysis system, chlortetracycline staining, and a fluorescent Ca2+ indicator. RESULTS: A comprehensive evaluation of sperm motility, especially hyperactivated motility, revealed that treatments with 40-320 µM ß-elemene decreased human sperm vitality, motility (total motility, progressive motility, and curvilinear velocity), and penetrating ability in a dose-dependent manner, but were non-toxic or minimally toxic toward MCF-10A, MDA-MD-231, and A549 cells. Although 10 and 20 µM ß-elemene did not affect sperm vitality and motility, these concentrations increased the spontaneous acrosome reaction and inhibited progesterone-induced sperm functions by affecting sperm [Ca2+]i. CONCLUSION: These results suggest that ß-elemene inhibits human sperm function by affecting sperm vitality and [Ca2+]i. These observations must be considered when using ß-elemene to treat cancer patients who may wish to preserve their fertility.

Rosmarinic acid compromises human sperm functions by an intracellular Ca2+ concentration-related mechanism.

Rosmarinic acid (RA), a natural phenolic ester, is cytoprotective for male reproduction in animal models. The present study investigated the in vitro actions of RA on human sperm functions. Human sperm were exposed to 1, 10, 100, and 1000 µM RA in vitro and sperm functions were examined. The results showed that although RA did not affect human sperm viability, RA at 10-1000 µM dose-dependently reduced sperm motility, penetration ability, capacitation, and spontaneous acrosome reaction. In addition, the intracellular Ca2+ concentration ([Ca2+]i), which serve as a key regulator of sperm function, was decreased by RA (10-1000 µM) in a dose-dependent manner. Furthermore, the current of the sperm-specific potassium channel, KSPER, which is predominant for Ca2+ influx in sperm, was dose-dependently inhibited by 10-1000 µM RA. Therefore, we conclude that in vitro exposure to RA can compromise human sperm functions by decreasing sperm [Ca2+]i through the suppression of KSPER current.