Subchronic exposure to arsenic inhibits spermatogenesis and downregulates the expression of ddx3y in testis and epididymis of mice

Toxicol Sci. 2012 Aug;128(2):482-9. doi: 10.1093/toxsci/kfs169. Epub 2012 May 10.

Abstract

Arsenic (As) is a ubiquitous environmental contaminant. Excess As exposure is considered one of the top health threats worldwide. As-induced Male reproductive toxicity is causing wide concern. The goal of this study is to determine whether subchronic As exposure inhibits Ddx3y expression, an Y-linked gene important in spermatogenesis and sperm maturation, and whether the inhibited expression of Ddx3y is closely associated with As-induced male reproductive toxicity Adult mice were given drinking water alone or water containing 1, 2, and 4mg/l arsenic trioxide (As(2)O(3)) for 60 days. After the treatment, the weights of testis and epididymis were analyzed. The sperm quality, spermatogenesis, and histological alteration of the testis and epididymis were observed by microscope. Furthermore, the expressions of Ddx3y gene and its protein in the testis and epididymis were examined by real-time reverse transcription PCR, Western blotting, and immunohistochemistry. Compared with untreated mice, the weights of testis and epididymis were reduced, sperm motility and the number of stage VII cells in the seminiferous epithelium section were decreased, sperm malformation ratio was increased, and histopathological alterations were observed in As-treated mice. The gene and protein expression of Ddx3y in testis and epididymis were significantly downregulated in As-exposed mice. Subchronic As exposure has detrimental effects on spermatogenesis and sperm development. It also downregulates Ddx3y expressions in testis and epididymis. Our results indicated that Ddx3y may be an important target gene of As and the downregulated expression of Ddx3y may be closely related to male reproductive toxicity induced by As.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenic / toxicity*
  • Base Sequence
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • DNA Primers
  • Down-Regulation / drug effects*
  • Epididymis / drug effects*
  • Epididymis / metabolism
  • Immunohistochemistry
  • Male
  • Mice
  • Minor Histocompatibility Antigens
  • Organ Size / drug effects
  • Real-Time Polymerase Chain Reaction
  • Spermatogenesis / drug effects*
  • Testis / drug effects*
  • Testis / metabolism

Substances

  • DNA Primers
  • Minor Histocompatibility Antigens
  • Ddx3y protein, mouse
  • DEAD-box RNA Helicases
  • Arsenic