PUMA regulates germ cell loss and primordial follicle endowment in mice.
- Myers, M; Morgan, H; Leiw, SH; Zerafa, N; Gamage, TU; Sarraj, M; Cook, M; Kapic, I; Sutherland, A; Scott, CL; Strasser, A; Findlay, JK; Kerr, JB; Hutt, KJ;
- Journal Title
- Publication Type
- JOURNAL ARTICLE
- The number of primordial follicles initially established within the ovary is influenced by the extent of germ cell death during foetal ovarian development, but the mechanisms that mediate this death have not been uncovered. We have identified PUMA, a pro-apoptotic BH3-only protein belonging to the BCL-2 family, as a critical determinant of germ cell number during ovarian development. Targeted disruption of the Puma gene revealed a significant increase in germ cell number as early as embryonic day (E) 13.5. Germ cell numbers remained elevated in Puma-/- compared to wild type (wt) females throughout the remainder of embryonic and early postnatal life, resulting in a 1.9-fold increase in the number of primordial follicles in the ovary at postnatal day (PN) 10. The increase in germ cell numbers observed in Puma-/- ovaries could not be attributed to altered germ cell proliferative activity within the ovary. Furthermore, PUMA was shown not to be required for the massive germ cell loss that occurs during germ cell nest breakdown. Our data suggest that PUMA is a critical regulator of germ cell death that acts during the migratory phase of oogenesis or very soon after the arrival of germ cells in the gonad, and that PUMA-mediated cell death limits the number of primordial follicles established in the initial ovarian reserve.
- Society for Reproduction and Fertility
- WEHI Research Division(s)
- Stem Cells And Cancer; Molecular Genetics Of Cancer
- Publisher's Version
- Copyright © 2014 by the Society for Reproduction and Fertility
Creation Date: 2014-05-28 07:35:44