Aims: AMH is deemed to inhibit the activation of the primordial follicle to begin follicle development. However, recent studies suggest that AMH has a stronger effect on inhibiting the progression of primary follicles to the secondary stage1,2. This study aimed to (1) determine if primary follicle survival was higher in Amh−/− mice and (2) examine whether AMH over-expressing mice exhibit higher rates of primary follicle atresia.
Methods: Primordial, transitioning, primary, secondary and antral follicle counts were counducted on histological ovary sections from Amh+/+ and Amh−/− mice. Active Casapase-3 immunohistochemistry was conducted on wild-type and AMH-overexpressing (Thy1.2-AMHTg/0) mouse ovaries to search for evidence of increased primary follicle atresia.
Results: AMH deficiency in 100-120 day-old mice caused a lower primordial follicle number but a higher activation rate. Meanwhile, a significant increase in primary, secondary, small antral, and medium antral follicle counts was found in Amh−/− mice compared with wild-type animals, indicating differing rates of developing follicle atresia between genotypes. The caspase-3 staining revealed high rates of atresia in late primary/early secondary follicles of Thy1.2-AMHTg/0 mice.
Conclusion: Results below show that AMH mediates preantral follicle loss and is a predominant influence on small antral follicle numbers, in addition to inhibiting primordial follicle activation during folliculogenesis. This new finding suggests that the role of AMH is not to conserve the ovarian reserve to prolong fertility but instead to prevent the antral follicle pool from becoming too large.
1 Pankhurst, M. W. et al. Anti-Mullerian hormone overexpression restricts preantral ovarian follicle survival. J Endocrinol 237, 153-163, doi:10.1530/joe-18-0005 (2018).
2 Kano, M. et al. AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy. Proc Natl Acad Sci U S A 114, E1688-E1697, doi:10.1073/pnas.1620729114 (2017).