The effect of mono-(2-ethylhexyl) phthalate on apoptosis of rat ovarian granulosa cells in vitro.

Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is considered to be a reproductive toxicant. This study was performed to evaluate the effect of MEHP on apoptosis of rat ovarian granulosa cells and explore potential mechanism. Granulosa cells were treated with MEHP (0, 25, 50, and 100 μmol/l). Inhibited cell viability and increased apoptosis rate were observed in 50 and 100 μmol/l groups. CASPASE3 activity and BAX expression were significantly raised in all MEHP-treated groups; BCL2 expression was elevated in 25 μmol/l group, while inhibited in 50 and 100 μmol/l groups; BAX/BCL2 ratio was increased in a typical dose-effect relationship. In conclusion, this study showed that MEHP exposure induced cell viability decrease and apoptosis, associated with increase of CASPASE3 activity and BAX/BCL2 ratio. Moreover, CASPASE3 activity showed a reversed dose-dependent effect in MEHP-treated groups, indicating there might exist other CASPASE-independent pathway involved in MEHP-induced apoptosis.