Impaired Functions of Human Granulosa Cell Line COV434 under Hypoxic and Inflammatory Conditions

Abstract

Premature ovarian insufficiency (POI) affects 1% of women under 40 years old and represents one of the main causes of infertility in females of childbearing age. POI is a primary ovarian defect resulting from follicular depletion and/or ovarian dysfunction caused by a compromised ovarian somatic cell compartment. Etiologically, ovarian dysfunction could be caused by certain diseases, including infections and autoimmune disorders. There could also be iatrogenic factors such as chemotherapy, radiation, or surgery. The related surgical risks are due to the possibility of disrupting the blood supply to the ovary and/or a subsequent inflammatory reaction. To date, it is unclear whether and how the impaired oxygen delivery and inflammatory environment may influence the basic functions of human ovarian somatic cells. In this study, we used an immortalized human granulosa cell line (COV434) as a model to investigate the effect of exposure to low oxygen levels (hypoxia) and inflammatory conditions on granulosa cell proliferation, apoptosis, and steroidogenesis. The results showed that both hypoxia (5% O₂) and proinflammatory cytokine treatment (a combination of TNF-α, IL-1β, IFN-γ and IL-6) significantly increased apoptosis, suppressed proliferation, and affected estradiol secretion in COV434 cells. Our data suggest that granulosa cells could be particularly sensitive to changes in the local environment caused by oxygen deprivation and chronic inflammation.