AMH TYPE II RECEPTOR DEFICIENT MICE DISPLAY A MORE SEVERE OVARIAN PHENOTYPE THAN AMH DEFICIENT MICE

Abstract

Anti-Mullerian hormone (AMH) is a member of the transforming growth factor beta family and signals through a specific type II receptor (AMHRII). Previously we have shown that in ovaries of AMH-deficient mice more primordial follicles are recruited, resulting in a larger pool of growing follicles. As a consequence of the increased rate of recruitment, the primordial follicle pool is depleted at an earlier age than in wild type mice. Similar to AMH, the AMHRII is expressed in granulosa cells of healthy preantral and small antral follicles. Furthermore, AMHRII is expressed in theca cells of these follicles, and expression in the pregranulosa cells of primordial follicles is suggested. To determine the role of the type II receptor in ovarian function, we have analyzed the follicle pool of AMHRII-deficient mice. In 13-month-old AMHRII null mice, the primordial follicle pool was completely depleted and as a consequence significantly less growing follicles (10-fold) were present compared to wild type mice. Ovaries of 4-month-old AMHRII null mice displayed a 3-fold increase in number of small growing follicles whereas the number of primordial follicles was decreased compared to wild type mice. These results suggest that primordial follicle recruitment is enhanced in AMHRII null mice, resembling the AMH null ovarian phenotype. However, the decrease in number of primordial follicles was more pronounced in AMHRII- than AMH-deficient mice at 4 months of age. Furthermore, whereas in AMH-deficient mice the number of primordial follicles did not differ between wildtype and null mice at 25 days of age, ovaries of AMHRII-deficient mice contained significantly less primordial follicles. This suggests that AMHRII may have an AMHindependent role in the ovary. In conclusion, AMHRII-deficient mice display a more severe ovarian phenotype than AMH-deficient mice. Studies are ongoing to determine whether enhanced recruitment alone is sufficient to explain the ovarian phenotype of the AMHRII null mice, or whether other mechanisms also contribute to the smaller primordial pool in AMHRII null mice. (poster)