Cobalt chloride, a hypoxia-mimicking agent, modulates redox status and functional parameters of cultured swine granulosa cells
Francesca Grasselli A B , Giuseppina Basini A , Simona Bussolati A and Federico Bianco AA Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti-Sezione di Fisiologia Veterinaria, Università di Parma, 43100 Parma, Italy.
B Corresponding author. Email: francesca.grasselli@unipr.it
Reproduction, Fertility and Development 17(7) 715-720 https://doi.org/10.1071/RD05059
Submitted: 20 May 2005 Accepted: 16 September 2005 Published: 2 November 2005
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 (CoCl2), 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 O2 sensing, ROS levels and scavenging enzyme activity were investigated. In the present study, CoCl2 had no effect on progesterone production, although it significantly reduced oestradiol synthesis. The addition of CoCl2 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.
Extra keywords: reactive oxygen species, steroidogenesis, vascular endothelial growth factor.
Acknowledgments
This work was supported by a FIL University of Parma grant and a ‘Programma di Ricerca di Rilevante Interesse Nazionale’ of the Ministero dell’Istruzione dell’ Università e della Ricerca.
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