Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo

Zilong Sun1, Ruiyan Niu, Bin Wang

  • 1Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, People's Republic of China.

Archives of Toxicology
|February 23, 2011
PubMed

Insights

Fluoride exposure damages sperm quality by increasing oxidative stress and apoptosis, leading to reduced fertility in mice. Molecular analysis revealed significant changes in gene expression related to sperm function.

Area of Science:

  • Reproductive Toxicology
  • Environmental Health
  • Molecular Biology

Background:

  • Fluoride exposure is linked to reduced sperm quality, but the underlying molecular mechanisms remain unclear.
  • Understanding these mechanisms is crucial for assessing reproductive risks associated with environmental fluoride.
  • Spermatozoa are particularly vulnerable to oxidative damage and apoptosis.

Purpose of the Study:

  • To investigate the effects of sodium fluoride (NaF) on sperm ultrastructure, oxidative stress, and apoptosis in mice.
  • To characterize the molecular changes in mouse sperm gene expression following fluoride exposure using microarray analysis.
  • To elucidate the mechanisms of fluoride-induced sperm damage and its impact on fertility.

Main Methods:

  • Mice were exposed to 150 mg/l NaF for 49 days.
  • Sperm were analyzed for ultrastructural changes, reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), and apoptosis.
  • Protein expression of cytochrome c and active caspase-3 was assessed.
  • Microarray analysis was performed to profile global gene expression in sperm.

Main Results:

  • Fluoride-exposed sperm exhibited increased ROS, decreased TAC, morphological abnormalities, and significant apoptosis.
  • Elevated protein levels of cytochrome c and active caspase-3 were observed in the fluoride group.
  • Microarray analysis identified 34 up-regulated and 63 down-regulated genes involved in critical sperm functions.
  • Affected pathways included signal transduction, oxidative stress, apoptosis, and sperm capacitation.

Conclusions:

  • Excessive ROS-induced oxidative stress likely triggers sperm apoptosis via mitochondrial impairment, leading to decreased fertility in fluoride-exposed mice.
  • Gene expression profiling provides valuable insights into the molecular pathways affected by fluoride toxicity in sperm.
  • These findings highlight the detrimental effects of fluoride on sperm morphology and function, necessitating further investigation.