Effect of nickel (Ni2+) on primary human ovarian granulosa cells in vitro

Csaba Révész, Zsolt Forgács, Péter Lázár, Szabolcs Mátyás, Klára Rajczy, Ferenc Krizsa, Artúr Bernard, István Gáti

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4 Citations (Scopus)


Human ovarian granulosa cells obtained from women undergoing in vitro fertilization were exposed to 15.6, 31.25, 62.5, 125, 250, 500, 1000 μM Ni2+ for 48 h. To determine the site of action of Ni2+, the granulosa cells were stimulated to produce progesterone (P) by using maximally stimulating amounts of human chorionic gonadotropin (0.1 IU/ml hCG) or dibutyryl cyclic adenosine monophosphate (1 mM db-cAMP). The luteinizing hormone (LH) analog hCG was chosen because resultant P production requires an intact membrane receptor and db-cAMP was used to test for post LH receptor defects caused by Ni2+. Progesterone content of the culture medium was determined by radioimmunoassay (RIA), and viability of the cells was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction test. Concentration-dependent depression in both hGC and db-cAMP stimulated P production was seen at 15.625 μM or higher concentration of Ni2+, which is not cytotoxic on human ovarian granulosa cells. The viability of cells was unaffected up to 31.25 μM and decreased significantly at 62.5 μM. Our results show a dose-related depression in stimulated P production of granulosa cells at a dose that does not induce significant cytotoxic action. These data indicate that the effect of Ni2+ on P production is not due to cytotoxicity, and the cellular site(s) of inhibitory action appears to be subsequent to the membrane receptor and production of cAMP.

Original languageEnglish
Pages (from-to)287-292
Number of pages6
JournalToxicology Mechanisms and Methods
Issue number5
Publication statusPublished - Sep 1 2004


  • Cytotoxicity
  • Granulosa cells
  • MTT
  • Nickel
  • Progesterone
  • cAMP
  • hCG

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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    Révész, C., Forgács, Z., Lázár, P., Mátyás, S., Rajczy, K., Krizsa, F., Bernard, A., & Gáti, I. (2004). Effect of nickel (Ni2+) on primary human ovarian granulosa cells in vitro. Toxicology Mechanisms and Methods, 14(5), 287-292. https://doi.org/10.1080/15376520490434566