Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA, 93106, USA.
Nat Commun. 2022 Feb 7;13(1):711. doi: 10.1038/s41467-022-28347-z.
In many species including humans, aging reduces female fertility. Intriguingly, some animals preserve fertility longer under specific environmental conditions. For example, at low temperature and short day-length, Drosophila melanogaster enters a state called adult reproductive diapause. As in other stressful conditions, ovarian development arrests at the yolk uptake checkpoint; however, mechanisms underlying fertility preservation and post-diapause recovery are largely unknown. Here, we report that diapause causes more complete arrest than other stresses yet preserves greater recovery potential. During dormancy, germline stem cells (GSCs) incur DNA damage, activate p53 and Chk2, and divide less. Despite reduced niche signaling, germline precursor cells do not differentiate. GSCs adopt an atypical, suspended state connected to their daughters. Post-diapause recovery of niche signaling and resumption of division contribute to restoring GSCs. Mimicking one feature of quiescence, reduced juvenile hormone production, enhanced GSC longevity in non-diapausing flies. Thus, diapause mechanisms provide approaches to GSC longevity enhancement.
在包括人类在内的许多物种中,衰老会降低女性的生育能力。有趣的是,一些动物在特定的环境条件下可以保持更长时间的生育能力。例如,在低温和短日照条件下,黑腹果蝇进入一种称为成虫生殖滞育的状态。与其他应激条件一样,卵黄摄取检查点会导致卵巢发育停止;然而,生育能力保存和滞育后恢复的机制在很大程度上尚不清楚。在这里,我们报告说,滞育比其他应激更彻底地停止,但保留了更大的恢复潜力。在休眠期间,生殖干细胞 (GSCs) 会产生 DNA 损伤,激活 p53 和 Chk2,并减少分裂。尽管龛信号减少,生殖前体细胞不会分化。生殖细胞祖细胞采用与女儿相连的非典型暂停状态。休眠后龛信号的恢复和分裂的恢复有助于恢复 GSCs。模拟静止的一个特征,即减少保幼激素的产生,增强了非滞育蝇的 GSC 寿命。因此,滞育机制为 GSC 长寿增强提供了途径。