PI3K signaling is proposed to regulate mEH expression. (A) VCD and DMBA both cause depletion of primordial follicles, however, (B) inhibition of PI3K signaling repressed VCD-induced but accelerated DMBA-induced ovotoxicity (Keating et al., 2009). These events are proposed to be due to increased mEH expression (B) since mEH is proposed to detoxify VCD, and is known to bioactivate DMBA (Igawa et al., 2009). Thus, the divergent levels of ovotoxicity observed due to inhibited PI3K signaling during VCD and DMBA exposure are hypothesized to be due to increased detoxification of VCD, but increased bioactivation of DMBA.