抄録
Gender-specific effect is widely existed, but the shortage of appropriate model restricts the study of gender-specific effect developmentally. Embryonic stem cell test (EST) has been utilized as an alternative test for developmental toxicity; despite numerous improvements to the EST, female mouse embryonic stem cells (ESC) has not been used in this test previously.
Therefore, in current study, a SP3 ESC with XX karyotype was applied to establish a “female” EST, while R1 ESC with XY karyotype was used as a “male” control, which allows testing of teratogenicity potential following chemicals exposure and their effect on each gender. Pluripotency determination and karyotype analysis were performed to assure the cellular quality of ESCs, and cardiac specific morphological and molecular endpoints were detected to monitor cardiac differentiation. A panel of test chemicals was selected for EST establishment, in which chemicals with different teratogenicity potential in vivo and without known gender-specific effect were chosen; classical microscopy observation, together with molecular endpoints Myh6 and cTnT were used to determine chemically induced embryotoxicity. The “female” EST could predict the embryotoxicity of this panel of chemicals correctly, as the “male” EST did. In addition, another three test chemicals with known gender-specific effect were assessed; an index was constructed for comparison between “male” and “female” EST, which would suggest if any gender-specific effect existed preliminarily. Endocrine disruptors with known gender-specific effect were predicted applying the “two genders” mouse EST, and their gender-specific effect could be distinguished.
