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Human Reproduction, Vol. 18, No. 2, 433-436, February 2003
© 2003 European Society of Human Reproduction and Embryology

Effect of various doses of gestogens on micronuclei frequency in human peripheral blood lymphocytes of pregnant women

Olivera Milosevic-Ðordevic1,4, Darko Grujicic1, Dragoslav Marinkovic2, Slobodan Arsenijevic3 and Smilja Bankovic3

1 Faculty of Science, Institute of Biology, Department of Genetics, University of Kragujevac, Radoja Domanovica 12, P.O. Box 60, 34000 Serbia, Kragujevac, 2 Faculty of Biology, Belgrade, and 3 Clinic of Gynecology, Kragujevac, Yugoslavia 4 To

whom To whom correspondence should be addressed. e-mail: olivera@knez.uis.kg.ac.yu

BACKGROUND: Since gestogens, in the form of hormonal substitution therapy, have been proposed to have a role in the prevention of threatened spontaneous abortions during the first three months of pregnancy, we decided to evaluate possible genotoxic effects of these preparations. METHODS: A total of 30 pregnant women, with a diagnosis of threatened spontaneous abortions, received the gestogen therapy in the first 3 months, and a sample of 30 pregnant women without indication for hormonal therapy were included as the control group. For investigation of mutagenic effects of gestogens in vivo the cytokinesis block (CB) micronucleus (MN) test was applied. RESULTS: Average MN frequency in the control group was 6.79 ± 0.69 MN/1000 cells. The second analysed group included 12 patients with threatened spontaneous abortions, who received gestogen therapy in doses of 100–750 mg. Average MN frequency in these patients before therapy was 11.83 ± 1.33 MN/1000 cells, and after therapy it was 16.50 ± 1.32 MN/1000 cells (P < 0.001). The third analysed group comprised nine patients, who received gestogen therapy in doses of 750–2000 mg. Average MN frequency in these patients before therapy was 15.67 ± 3.00 MN/1000 cells, and after therapy was 23.89 ± 2.49 MN/1000 cells (P < 0.001). The fourth analysed sample comprised nine patients, treated with gestogen doses of 2000–8400 mg. The average MN frequency in these patients before therapy was 11.89 ± 1.63 MN/1000 cells, and after therapy was 21.22 ± 2.80 MN/1000 cells (P < 0.001). CONCLUSIONS: The increase of therapeutic gestogen doses was followed by an increase of average MN frequency. The greatest rise of MN frequency (1.8-fold) was observed in the group of patients who were treated with the highest gestogen doses (2000–8400 mg). The smallest increase (1.4-fold) of MN frequency was found in the group of patients whose therapeutic doses were the lowest (100–750 mg).

Key words: genotoxicity/gestogens/micronuclei/peripheral blood lymphocytes/pregnancy


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