Genistein effect in cultured ovine ovarian granulosa cells

Genistein, an isoflavone has the potential to mimic, augment, or dysregulate the steroid hormone production pathways. We hypothesized that genistein affects the granulosa cell (GCs) functions through a series of biochemical, molecular, and genomic cascades. The present study was conducted to evaluate the impact of genistein exposure on GCs viability, apoptosis, and steroidogenesis. The present study involved 3/5 days of exposure to genistein on GCs collected from abattoir-derived ovine ovaries at doses of 0, 1, 10, 25, 50, and 100 mu M. The harvested GCs were used for growth, cytotoxicity, and gene expression studies related to apoptosis, growth, and steroidogenesis. We observed that genistein had both stimulatory at 10 and 25 mu M levels as well as inhibitory effects at 50 and 100 mu M levels on the growth and proliferation of GCs. Genistein significantly decreased the levels of 17 beta-estradiol at higher exposure (50 and 100 mu M), whereas the progesterone level increased significantly as the genistein exposure increased. Additionally, genistein could also alter the mRNA expression of the steroidogenic receptor, enzymes, proteins, and growth-related genes suggesting that genistein could potentially alter the steroidogenic pathways. We conclude that genistein can interfere with cell survival and steroidogenesis by exhibiting a dose-dependent biphasic response on the viability, growth-related parameters, and the synthesis of 17 beta-estradiol in the cultured GCs. Present study reveals that Genistein may exhibit great potential to evoke a biphasic response at specific doses in ovine ovarian granulosa cells and thus can alter cell viability, 17-estradiol progesterone synthesis, promote apoptosis. All these parameters may result in ovarian cellular toxicity through the alteration of genomic pathways. image