Inhibin B response to testicular toxicants hexachlorophene, ethane dimethane sulfonate, di-(n-butyl)-phthalate, nitrofurazone, DL-ethionine, 17-alpha ethinylestradiol, 2,5-hexanedione, or carbendazim following short-term dosing in male rats

Birth Defects Res B Dev Reprod Toxicol. 2013 Feb;98(1):41-53. doi: 10.1002/bdrb.21035. Epub 2013 Jan 24.

Abstract

Background: Inhibin B is a heterodimer glycoprotein that downregulates follicle-stimulating hormone and is produced predominantly by Sertoli cells. The potential correlation between changes in plasma Inhibin B and Sertoli cell toxicity was evaluated in male rats administered testicular toxicants in eight studies. Inhibin B fluctuations over 24 hr were also measured.

Methods: Adult rats were administered one of eight testicular toxicants for 1 to 29 days. The toxicants were DL-ethionine, dibutyl phthalate, nitrofurazone, 2,5-hexanedione, 17-alpha ethinylestradiol, ethane dimethane sulfonate, hexachlorophene, and carbendazim. In a separate study plasma was collected throughout a 24-hr period via an automatic blood sampler.

Results: Histomorphologic testicular findings included seminiferous tubule degeneration, round and elongate spermatid degeneration/necrosis, seminiferous tubule vacuolation, aspermatogenesis, and interstitial cell degeneration. There was a varying response of plasma Inhibin B levels to seminiferous tubule toxicity, with three studies showing high correlation, three studies with a response only at a certain time or dose, and two studies with no Inhibin B changes. In a receiver operating characteristics exclusion model analysis, where treated samples without histopathology were excluded, Inhibin B showed a sensitivity of 70% at 90% specificity in studies targeting seminiferous tubule toxicity.

Conclusion: Decreases in Inhibin B correlated with Sertoli cell toxicity in the majority of studies evaluated, demonstrating the value of Inhibin B as a potential biomarker of testicular toxicity. There was no correlation between decreases in Inhibin B and interstitial cell degeneration. In addition, a pattern of Inhibin B secretion could not be identified over 24 hr.

MeSH terms

  • Animals
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / toxicity
  • Carbamates / administration & dosage
  • Carbamates / toxicity
  • Dibutyl Phthalate / administration & dosage
  • Dibutyl Phthalate / toxicity
  • Environmental Pollutants / administration & dosage*
  • Environmental Pollutants / toxicity*
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / toxicity
  • Ethionine / administration & dosage
  • Ethionine / toxicity
  • Hexachlorophene / administration & dosage
  • Hexachlorophene / toxicity
  • Hexanones / administration & dosage
  • Hexanones / toxicity
  • Inhibins / blood*
  • Male
  • Mesylates / administration & dosage
  • Mesylates / toxicity
  • Nitrofurazone / administration & dosage
  • Nitrofurazone / toxicity
  • ROC Curve
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Testis / drug effects
  • Testis / pathology

Substances

  • Benzimidazoles
  • Carbamates
  • Environmental Pollutants
  • Hexanones
  • Mesylates
  • inhibin B
  • Dibutyl Phthalate
  • Ethinyl Estradiol
  • Inhibins
  • 2,5-hexanedione
  • ethylene dimethanesulfonate
  • carbendazim
  • Hexachlorophene
  • Ethionine
  • Nitrofurazone