Effects of blue-green algal toxin cylindrospermopsin (CYN) on human granulosa cells in vitro

The blue-green algal toxin cylindrospermopsin (CYN) occurs in public water supplies. CYN was hepatotoxic when administered orally to mice, and cytotoxic and genotoxic to human cell lines. To determine the effects of CYN on primary human IVF-derived granulosa cells, 0-1 μg/ml CYN was added to cells for 2, 4 or 6 h ± hCG (n = 6), or for 24, 48 and 72 h (n = 6). Cytotoxicity was evaluated by MTT assay, and secreted progesterone or estrogen quantified by radioimmunoassay. 24 h exposure to 1 μg/ml CYN was cytotoxic (p < 0.05), whereas 0.0625 μg/ml CYN did not cause cytotoxicity or affect estrogen production, but did inhibit basal progesterone production (p < 0.01). Similarly, 6 h exposure to 1 μg/ml CYN did not affect cytotoxicity or hCG-stimulated estrogen production, but did inhibit hCG-stimulated progesterone production (p < 0.01). In this in vitro assay, CYN inhibited progesterone production and therefore has the potential to be an endocrine disrupter by changing the progesterone:estrogen ratio in women.