Chromium-VI arrests cell cycle and decreases granulosa cell proliferation by down-regulating cyclin-dependent kinases (CDK) and cyclins and up-regulating CDK-Inhibitors

摘要

Environmental contamination with hexavalent chromium (CrVI) has been increasing in the drinking water of the USA and developing countries. CrVI causes various health problems including menstrual disorders and infertility. Recently, we reported that CrVI causes granulosa cell apoptosis through the intrinsic apoptotic pathway. Our previous studies showed that postnatal exposure to CrVI arrests follicle development. In order to explore the underlying mechanism, primary and immortalized granulosa cells from rats were treated with 10 μM potassium dichromate and analyses of the cell cycle, and cell cycle regulatory proteins were performed. CrVI decreased cell proliferation as a result of cell cycle arrest and down-regulated cyclin-dependent kinases (CDK), cyclins, and PCNA while up-regulating CDK-inhibitors and down-regulating FSH receptor and ERβ. Vitamin C mitigated the effects of CrVI. This study shows that CrVI causes cell cycle arrest in granulosa cells by altering cell cycle regulatory proteins with potential intervention by vitamin C.