Survivin belongs to IAP family and is over-expressed in embryonic stem cells and malignant cancer cells. Several studies found that survivin was biologically important for oocyte development and maturation. In this work, we developed an in vitro three-dimensional fluorescent embryonic stem cell-based model for indentifying potential survivin modulators in high throughput manners. We hypothesized that decreased survivin expression might result in embryotoxic effects, which was tested and validated using a set of known non-embryotoxic (acrylamide), moderately embryotoxic (tetracycline and boric acid), and strongly embryotoxic drugs (retinoic acid, Ginkgo Biloba extract and methotrexate hydrate). It was found that strongly embryotoxic drugs significantly decreased survivin expression, while moderately embryotoxic drugs reduced survivin expression slightly. Additionally, it was found that acrylamide upregulated survivin expression due to its tumorigenic effects. These results showed that the HTS assay could serve as a reliable, sensitive and robust method to screen embryotoxic potential of chemical compounds.

High throughput screening of survivin expression modulators associated with cytotoxic and embryotoxic effects

243rd National Meeting (2012)

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