Generation of a potent AMH therapy for the preservation of female fertility

Anti-mullerian Hormone (AMH) or Mullerian Inhibiting Substance (MIS) is fundamentally known for its crucial activities in gonadal development during embryogenesis. Embryonic expression of AMH promotes regression of the female reproductive tract (mullerian ducts), resulting in development of the male gonads. In adulthood, AMH has pivotal roles in regulating ovarian, and to a lesser degree, testicular function. In adult females, AMH is made by the granulosa cells of the pre-antral and small antral follicles in the ovary. Consequently, circulating AMH is only detectable in women prior to the onset of menopause. AMH acts to restrict recruitment of these immature follicles, such that only the dominant follicle is recruited for maturation. Emerging evidence suggests that AMH supplementation could provide a means to preserve the follicle pool in women, whilst also providing contraceptive protection. However, development of AMH as a therapeutic agent is limited by a lack of knowledge on the structure of the bioactive form(s) of AMH, and poor understanding of how AMH exerts its signaling activity via its target cell surface receptor AMHRII. We are using targeted mutagenesis to understand how AMH exerts its signaling activity, and to generate potent AMH analogues as therapies for the preservation of female fertility.