Autor: |
Soygur B; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research and Department of Obstetrics, Gynecology and Reproductive Science, UCSF, San Francisco, CA 94143 USA., Gaylord EA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research and Department of Obstetrics, Gynecology and Reproductive Science, UCSF, San Francisco, CA 94143 USA., Foecke MH; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research and Department of Obstetrics, Gynecology and Reproductive Science, UCSF, San Francisco, CA 94143 USA., Cincotta SA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research and Department of Obstetrics, Gynecology and Reproductive Science, UCSF, San Francisco, CA 94143 USA., Horan TS; Department of Biomedical Sciences, Cornell Reproductive Sciences Center, Cornell University, Ithaca, NY 14853., Wood A; Department of Biomedical Sciences, Cornell Reproductive Sciences Center, Cornell University, Ithaca, NY 14853., Cohen PE; Department of Biomedical Sciences, Cornell Reproductive Sciences Center, Cornell University, Ithaca, NY 14853., Laird DJ; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research and Department of Obstetrics, Gynecology and Reproductive Science, UCSF, San Francisco, CA 94143 USA. |
Abstrakt: |
Ovulation results from the cyclical recruitment of non-renewing, quiescent oocytes for growth. Therefore, the primordial follicles that are established during development from an oocyte encapsulated by granulosa cells are thought to comprise the lifelong ovarian reserve 1-4 . However, using oocyte lineage tracing in mice, we observed that a subset of oocytes recruited for growth in the first juvenile wave remain paused for many months before continuing growth, ovulation, fertilization and development into healthy offspring. This small subset of genetically-labeled fetal oocytes, labeled with Sycp3-CreERT2, is distinguished by earlier entry and slower dynamics of meiotic prophase I. While labeled oocytes were initially found in both primordial follicles and growing follicles of the first wave, they disappeared from primordial follicles by puberty. Unexpectedly, these first-wave labeled growing oocytes persisted throughout reproductive lifespan and contributed to offspring at a steady rate beyond 12 months of age, suggesting that follicles can pause mid-growth for extended periods then successfully resume. These results challenge the conclusion from lineage tracing of granulosa cells that first-wave follicles make a limited contribution to fertility 5 and furthermore suggest that growth-paused oocytes comprise a second and previously unrecognized ovarian reserve. |