17α-Ethinylestradiol can disrupt hemoglobin catabolism in amphibians

Comp Biochem Physiol C Toxicol Pharmacol. 2015 May:171:34-40. doi: 10.1016/j.cbpc.2015.03.004. Epub 2015 Mar 25.

Abstract

Different chemical substances, which enter the environment due to anthropogenic influences, can affect the endocrine system and influence development and physiology of aquatic animals. One of these endocrine disrupting chemicals is the synthetic estrogen, 17α-ethinylestradiol (EE2), which is a main component of various oral contraceptives and demonstrably affects many different aquatic vertebrates at extremely low concentrations by feminization phenomena. The aim of the present study was to investigate whether a four week exposure to three different concentrations of EE2 (0.3 ng/L, 29.6 ng/L and 2960 ng/L) affects the catabolism of hemoglobin of the amphibian Xenopus laevis. The results of this study demonstrate for the first time that beside an increase of the hepatic vitellogenin gene expression, exposure to EE2 also decreases the gene expression of the hepatic heme oxygenase 1 and 2 (HO1, HO2), degrading heme of different heme proteins to biliverdin, as well as of the biliverdin reductase A (BLVRA), which converts biliverdin to bilirubin. The results further suggest that EE2 already at the environmentally relevant concentration of (29.6 ng/L) can disrupt hemoglobin catabolism, indicated by decreased gene expression of HO2, which becomes evident at the highest EE2 concentration that led to a severe increase of biliverdin in plasma.

Keywords: 17α-ethinylestradiol; Endocrine disrupting chemicals; Xenopus laevis; biliverdin; biliverdin reductase; estrogen; heme oxygenase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biliverdine / blood
  • Biliverdine / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Endocrine Disruptors / toxicity*
  • Estrogens / toxicity
  • Ethinyl Estradiol / toxicity*
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Hemoglobins / metabolism*
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Osmolar Concentration
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • RNA, Messenger / metabolism
  • Spleen / drug effects*
  • Spleen / enzymology
  • Spleen / metabolism
  • Vitellogenins / genetics
  • Vitellogenins / metabolism
  • Water Pollutants, Chemical / toxicity*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis / blood
  • Xenopus laevis / physiology*

Substances

  • Biomarkers
  • Endocrine Disruptors
  • Estrogens
  • Hemoglobins
  • RNA, Messenger
  • Vitellogenins
  • Water Pollutants, Chemical
  • Xenopus Proteins
  • Ethinyl Estradiol
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • heme oxygenase-2
  • Oxidoreductases Acting on CH-CH Group Donors
  • biliverdin reductase
  • Biliverdine