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

Cell Physiol Biochem. 2018;51(5):2019-2029. doi: 10.1159/000495821. Epub 2018 Dec 6.

Abstract

Background/aims: β-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 β-elemene on human sperm function and elucidate the underlying mechanism.

Methods: The cytotoxicity of β-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 β-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 β-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 β-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 β-elemene inhibits human sperm function by affecting sperm vitality and [Ca2+]i. These observations must be considered when using β-elemene to treat cancer patients who may wish to preserve their fertility.

Keywords: Acrosome reaction; Sperm motility; [Ca2+]I progesterone; β-elemene.

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Calcium / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • Humans
  • Male
  • Neoplasms / drug therapy
  • Sesquiterpenes / adverse effects*
  • Sesquiterpenes / pharmacology
  • Sperm Motility / drug effects
  • Spermatozoa / cytology
  • Spermatozoa / drug effects*

Substances

  • Antineoplastic Agents
  • Sesquiterpenes
  • beta-elemene
  • Calcium