Paraquat exposure delays stem/progenitor Leydig cell regeneration in the adult rat testis

Chemosphere. 2019 Sep:231:60-71. doi: 10.1016/j.chemosphere.2019.05.104. Epub 2019 May 16.

Abstract

Paraquat, a widely used nonselective herbicide, is a serious hazard to human health. However, the effects of paraquat on the male reproductive system remain unclear. In this study, adult male Sprague Dawley rats were intraperitoneally injected ethane dimethane sulfonate (EDS, 75 mg/kg) to initiate a regeneration of Leydig cells. EDS-treated rats were orally exposed to paraquat (0.5, 2, 8 mg/kg/day) from post-EDS day 17 to day 28 and effects of paraquat on Leydig and Sertoli cell functions on post-EDS day 35 and day 56 were investigated. Paraquat significantly decreased serum testosterone levels at 2 and 8 mg/kg. Paraquat lowered Leydig cell Hsd17b3, Srd5a1, and Hsd11b1 mRNA levels but increased Hsd3b1 on post-EDS day 35. Paraquat lowered Cyp11a1, Cyp17a1, and Hsd11b1 but increased Srd5a1 on post-EDS day 56. However, paraquat did not alter Leydig cell number and PCNA labeling index. Epididymal staining showed that few sperms were observed in paraquat-treated rats. Primary culture of adult Leydig cells showed that paraquat diminished testosterone output and induced reactive oxygen species generation at 1 and 10 μM and apoptosis rate at 10 μM. In conclusion, a short-term exposure to paraquat delays Leydig cell regeneration from stem/progenitor Leydig cells, causing low production of testosterone and an arrest of spermatogenesis.

Keywords: Differentiation; Leydig cell regeneration; Leydig cells; Paraquat; Reactive oxygen species; Steroidogenesis.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / analysis
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
  • 17-Hydroxysteroid Dehydrogenases / analysis
  • 17-Hydroxysteroid Dehydrogenases / genetics
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / analysis
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics
  • Animals
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects*
  • Herbicides / toxicity*
  • Leydig Cells / cytology*
  • Leydig Cells / drug effects
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Mesylates / pharmacology
  • Paraquat / toxicity*
  • Progesterone Reductase / analysis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Regeneration / drug effects*
  • Spermatogenesis / drug effects*
  • Steroid 17-alpha-Hydroxylase / analysis
  • Testosterone / blood

Substances

  • Herbicides
  • Membrane Proteins
  • Mesylates
  • RNA, Messenger
  • Reactive Oxygen Species
  • Testosterone
  • 17-Hydroxysteroid Dehydrogenases
  • Progesterone Reductase
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Steroid 17-alpha-Hydroxylase
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • Srd5a1 protein, rat
  • ethylene dimethanesulfonate
  • Paraquat