Fig. 2. Expression of KRAS^G12D in granulosa cells causes multiple reproductive defects. (A) Continuous breeding assay showing the cumulative number of progeny per female. The LSL-Kras^G12D;Amhr2-Cre and LSL-Kras^G12D;Cyp19-Cre females (n=6) were subfertile. (B) Superovulation experiments showing that the ovulation rate in response to gonadotropins was reduced in Kras mutant mice (n=10) as compared with the wild type (WT). (C-J) Histology of WT (C,E,G,I) and LSL-Kras^G12D;Amhr2-Cre (D,F,H,J) ovaries at 8 (C-F), 16 (G,H) and 48 (I,J) hours after hCG treatment. Histology of WT (I) and LSL-Kras^G12D;Amhr2-Cre (J) ovaries 48 hours after hCG treatment shows that an oocyte is trapped in the corpus luteum of the Kras mutant ovary (arrow).