Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, Yale School of Medicine, 333 Cedar Street FMB 329F, New Haven, CT 06520, USA.
Mol Hum Reprod. 2010 Dec;16(12):916-27. doi: 10.1093/molehr/gaq066. Epub 2010 Jul 22.
A great deal of evolutionary conservation has been found in the control of oocyte development, from invertebrates to women. However, little is known of mechanisms that control oocyte loss over time. Oocyte loss is often assumed to be a result of oocyte-intrinsic deficiencies or damage. In fruit flies, starvation results in halted oocyte production by germline stem cells and induces oocyte loss midway through development. When we fed wild-type flies the bacterial compound Rapamycin (RAP) to mimic starvation, production of new oocytes continued, but mid-stage loss sterilized the animals. Surprisingly, follicle cell invasion and phagocytosis of the oocyte preceded any signs of germ cell death. RAP-induced egg chamber loss was prevented when RAP receptor FKBP12 was knocked down specifically in follicle cells. Oogenesis continued past the mid-stages, and these mutants continued to lay embryos that could develop into normal adults. Hence, intact healthy oocytes can be destroyed by somatic cells responding to extrinsic stimuli. We termed this process inducible somatic oocyte destruction. RAP treatment of mouse follicles in vitro resulted in phagocytic uptake of the oocyte by granulosa cells as seen in flies. We hypothesize that extrinsic modes of oocyte loss occur in mammals.
从无脊椎动物到人类，卵母细胞发育的调控在很大程度上具有进化保守性。然而，对于控制卵母细胞随时间丢失的机制却知之甚少。卵母细胞丢失通常被认为是卵母细胞内在缺陷或损伤的结果。在果蝇中，饥饿导致生殖干细胞停止产生卵母细胞，并在发育中途诱导卵母细胞丢失。当我们用细菌化合物雷帕霉素（RAP）喂养野生型果蝇以模拟饥饿时，新卵母细胞的产生仍在继续，但中期损失使动物绝育。令人惊讶的是，滤泡细胞的侵袭和卵母细胞的吞噬作用先于任何生殖细胞死亡的迹象发生。当 RAP 受体 FKBP12 特异性敲低滤泡细胞时，RAP 诱导的卵囊中损失可以被阻止。卵母细胞的发生继续超过中期，这些突变体继续产卵，这些卵可以发育成正常的成虫。因此，完整健康的卵母细胞可以被对外界刺激作出反应的体细胞破坏。我们将这个过程称为诱导性体腔卵母细胞破坏。体外 RAP 处理小鼠卵泡导致卵母细胞被颗粒细胞吞噬，如在果蝇中所见。我们假设哺乳动物中存在外在的卵母细胞丢失模式。
