title: Cobalt chloride, a hypoxia-mimicking agent, modulates redox status and functional parameters of cultured swine granulosa cells.
abstract: Hypoxia occurs physiologically during ovarian follicle growth; this deprivation represents a triggering stimulus for the production of vascular endothelial growth factor (VEGF) by proliferating granulosa cells, which are mostly responsible for the growth of the follicle. Moreover, the steroidogenic activity of these cells ensures a receptive environment for the implantation and development of the early embryo. The present paper reports the adaptive response of swine granulosa cells to cobalt chloride (CoCl(2), a chemical hypoxia-mimicking agent. The effects of the treatment were evaluated on cell proliferation, steroidogenesis and VEGF production. In addition, because mithocondrial reactive oxygen species (ROS) are possibly involved in O(2) sensing, ROS levels and scavenging enzyme activity were investigated. In the present study, CoCl 2 had no effect on progesterone production, although it significantly reduced oestradiol synthesis. The addition of CoCl(2) to granulosa cell culture stimulated VEGF production and the generation of hydrogen peroxide. Chemical hypoxia had different effects on scavenger enzyme activities: the activity of superoxide dismutase was enhanced, that of peroxidase reduced and catalase activity was unaffected. The net result is a 'pro-oxidant' state, which appears to be possibly involved in the stimulation of VEGF production, thus inducing follicular angiogenesis.
authors.affiliation: Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti-Sezione di Fisiologia Veterinaria, Università di Parma, Italy. francessa.grasselli@unipr.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Grasselli
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Basini
authors.forename: Simona
authors.initials: S
authors.lastname: Bussolati
authors.forename: Federico
authors.initials: F
authors.lastname: Bianco
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D005260:Female; D042341:Gonadal Hormones / Q000096:biosynthesis; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D042341:Gonadal Hormones; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; C018021:cobaltous chloride