IRON OVERLOAD IN THE BODY AS ONE OF THE POSSIBLE CAUSES OF PREMATURE OVARIAN FAILURE

Objective. To study iron homeostasis in patients with premature ovarian failure (POF) at the systemic and tissue levels. Material and methods. A multistage investigation of iron metabolism was conducted in patients with POF at both the systemic and tissue levels, which encompassed molecular genetic testing of the HFE gene; determination of the biochemical parameters of iron metabolism (serum iron, transferrin, iron transferrin saturation ratio, ferritin); ovarian tissue histological and histochemical examinations; electron paramagnetic resonance spectroscopy of whole blood. Control groups were presented by 101 women with timely menopause to determine the polymorphisms of the HFE gene; 91 female donors to estimate the intensity of electron paramagnetic resonance signals, 9 ovarian tissue autopsy and biopsy specimens. Results. HFE gene mutations were found in 21.6% of the patients with POF and in 15.8% in the control group. Abnormal values of the biochemical parameters of iron metabolism were noted in 68.2% of the patients with HFE gene mutations. A spectral technique revealed non-transferrin-bound iron in 40.9% of the patients with HFE gene mutations; its level was similar to the baseline value in the control samples. The histological examination showed hemosiderin granules in 75% of the ovarian tissue samples from the POF patients with HFE gene mutations. Conclusion. Iron overload at the systemic and tissue levels with its further accumulation in the ovarian tissues may be one of the additional pathogenetic mechanisms of accelerated apoptosis of follicles, which lead to POF.

SNP, premature ovarian failure, hemochromatosis, iron overload, HFE gene mutation, electron paramagnetic resonance spectroscopy, single nucleotide polymorphism