Ultrastructural and morphometrical changes of mice ovaries following experimentally induced copper poisoning

Abstract

Background: Copper (Cu) is an essential trace element involved in normal reproduction but its over-exposure may produce some detrimental effects. The aim of this study was to investigate the effects of copper sulfate poisoning on morphometery of mice ovarian structures and probable intracellular changes. Methods: Thirty mature female mice were randomly allocated to control and two treatment groups. In treatment groups, two different doses of copper sulfate including 100 mg/kg and 200 mg/kg in 0.2 cc were applied once a day for 35 consecutive days by gavage. Control animals received normal saline using the same volume and similar method. Animals from each experimental group were sacrificed 14 and 35 days after the beginning of drug administration and the left ovaries were removed for stereological evaluations by light microscopy and right ovaries were obtained for preparing electron microscopic sections. Results: The morphometrical results showed that only the number of antral follicles was decreased by 100 mg/kg copper sulfate on day 14 compared to the control group (P=0.043). Hence, higher copper dose or longer consumption period significantly reduced different classes of follicles and corpora lutea. With 100 mg/kg copper sulfate some mild ultrastructural cell damages such as decrease of zona pellucida thickness, limited vacuolated areas and nuclear envelop dilation were seen on day 14. Higher or longer Cu administration produced more detrimental effects including more vacuolated areas, presence of secondary lysosomes, irregularity in cell shape and segmented nuclei with condensed and marginated chromatin and more enlarged and damaged mitochondria. Conclusion: New evidences of early as well as late intracellular damages of copper has been presented by accurate stereological and ultrastructural methods. Antral follicles was the most susceptible cells with the lower and shorter copper consumption and long term or higher dose of copper affected the whole of ovarian structures.