7. Copyright ©2001 The Endocrine Society

10. Follicular population in hyperprolific Booroola ewes Homozygous B/B Q249R Ovulation rate = 5 Size of ovulatory follicles = 3.5mm Wild type +/+ Q249 Ovulation rate = 1 Size of ovulatory follicles = 7mm Heterozygous +/B Q249 Q249R Ovulation rate = 3 Size of ovulatory follicles = 4.5mm

11. BMP system in ovine follicles BMPs inhibit progesterone secretion Progesterone (% of control) Control BMP-2 BMP-4 BMP-6 Act-A TGFb-1 0 20 40 60 80 100 120 Small follicles (1-3 mm) Preovulatory follicles (≥ 5 mm) Granulosa cell primary cultures small preovulatory Control BMP-4 P450scc Fabre et al, 2003

12. Biological effects of BMPR-IB ligands on +/+ and B/B granulosa cells in vitro Mulsant et al., 2001 Fabre et al, 2003 Progesterone synthesis +/+ B/B BMPR-IB Q249R : partial loss of responsiveness to BMP-4

13. Mérinos BB Mérinos B+Mérinos ++ E2 + + LH E2 + + LH E2 + + LH Figure. Représentation schématique de la rétroaction positive de l’oestradiol sur l’axe hypothalamo-hypophysaire : conséquences de la présence du gène Booroola. D’après McNatty et al. ( ), la production d’oestradiol par chaque follicule préovulatoire BB est inférieure à celle de l’unique follicule ++, mais la production de l’ensemble des follicules BB lui est équivalente.

14. Wild type ewes +/+ Ovulation rate = 1 BMP15 Heterozygous ewes BMP15 +/- Ovulation rate = 3 BMP15 Partial loss of function (50%) Ovarian Follicular population in hyperprolific Inverdale, Hanna, Cambridge and Lacaune ewes Inverdale : V31D Hanna : Q23STOP Cambridge : S77F and Q239STOP Lacaune : C53Y Homozygous ewes BMP15 -/- Sterile BMP15 Complete loss of function Galloway et al., 2000 Hanrahan et al., 2004 Bodin et al., 2004

15. Wild type ewes +/+ Ovulation rate = 1 Partial loss of function BMP15 +/- Booroola +/- Booroola -/- Ovulation rate = 3-5 Complete loss of function BMP15 -/- Ovulation rate = 0 Consequences of partial/complete loss of function of BMP-15 and BMPR-IB on follicular population and ovulation

18. Communication entre les voies de mort cellulaire Ligand de CD95 CD95 FADD Procaspase-8 Substrats apoptotiques Cytochrome c Procaspase-9 Apaf-1 Apoptosome DIABLO IAPs Caspase-3 Procaspase-3 AIF Bcl-x L Bax Bcl-2 c-FLIP Noyau p53 ADN endommagé Bid clivé Bid Caspase-8