Cylindrospermopsin, a blue-green algal toxin, inhibited human luteinised granulosa cell protein synthesis in vitro

The blue-green algal toxin cylindrospermopsin (CYN) inhibits protein synthesis, and CYP450 enzymes metabolise CYN to cytotoxic endproducts. Human chorionic gonadotrophin (hCG) stimulates the de novo synthesis of StAR and CYP450 aromatase. Human IVF-derived granulosa cells (GC) (n = 7) were exposed to 0–5 μM CYN ± 1 IU/ml hCG for 2–24 h. After 24 h pre-culture GC responded to hCG by increasing estradiol 17β (E2) and progesterone (P4) synthesis. Three micromolar of CYN ± 1 IU/ml hCG for 24 h was not cytotoxic and did not affect basal or hCG-stimulated E2 or P4 production, but did inhibit protein synthesis (p < 0.05, n = 4). hCG-stimulated steroidogenesis was not reduced by CYN, suggesting a lack of effect on StAR or CYP450 aromatase protein synthesis. hCG enhanced the effects of CYN on GC protein synthesis. Twenty four hours exposure to 0.1 μM CYN did not affect GC, supporting the establishment of a 0.0024 μM Guideline level for CYN in public water supplies.

► The blue green algal toxin cylindrospermopsin (CYN) inhibits protein synthesis.
► Chorionic gonadotrophin (hCG) stimulates StAR protein synthesis which increases granulosa cell steroidogenesis.
► CYN inhibited granulosa protein synthesis but not hCG-stimulated steroidogenesis.
► IVF-derived granulosa cells from infertile women were more sensitive to CYN toxicity than the cells from fertile women.