MRC Human Reproductive Sciences Unit, Queen's Institute of Medical Research, Centre for Reproductive Biology Obstetrics and Gynaecology, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
Reproduction. 2011 Jun;141(6):821-31. doi: 10.1530/REP-10-0327. Epub 2011 Mar 10.
Macrophages are the most abundant immune cell within the ovary. Their dynamic distribution throughout the ovarian cycle and heterogenic array of functions suggest the involvement in various ovarian processes, but their functional role has yet to be fully established. The aim was to induce conditional macrophage ablation to elucidate the putative role of macrophages in maintaining the integrity of ovarian vasculature. Using the CD11b-diphtheria toxin receptor (DTR) mouse, in which expression of human DTR is under the control of the macrophage-specific promoter sequence CD11b, ovarian macrophages were specifically ablated in adult females by injections of diphtheria toxin (DT). CD11b-DTR mice were given DT treatment or vehicle and ovaries collected at 2, 8, 16, 24 and 48 h. Histochemical stains were employed to characterise morphological changes, immunohistochemistry for F4/80 to identify macrophages and the endothelial cell marker CD31 used to quantify vascular changes. In normal ovaries, macrophages were detected in corpora lutea and in the theca layer of healthy and atretic follicles. As macrophage ablation progressed, increasing amounts of ovarian haemorrhage were observed affecting both luteal and thecal tissue associated with significant endothelial cell depletion, increased erythrocyte accumulation and increased follicular atresia by 16 h. These events were followed by necrosis and profound structural damage. Changes were limited to the ovary, as DT treatment does not disrupt the vasculature of other tissues likely reflecting the unique cyclical nature of the ovarian vasculature and heterogeneity between macrophages within different tissues. These results show that macrophages play a critical role in maintaining ovarian vascular integrity.
巨噬细胞是卵巢中最丰富的免疫细胞。它们在卵巢周期中的动态分布和异质性的功能阵列表明它们参与了各种卵巢过程，但它们的功能作用尚未完全确定。本研究旨在诱导条件性巨噬细胞消融，以阐明巨噬细胞在维持卵巢血管完整性中的潜在作用。使用 CD11b-白喉毒素受体 (DTR) 小鼠，其中人 DTR 的表达受巨噬细胞特异性启动子序列 CD11b 的控制，通过注射白喉毒素 (DT) 特异性消融成年雌性小鼠的卵巢巨噬细胞。CD11b-DTR 小鼠接受 DT 处理或载体处理，并在 2、8、16、24 和 48 小时收集卵巢。采用组织化学染色来描述形态学变化，用 F4/80 免疫组化鉴定巨噬细胞，用 CD31 标记内皮细胞来量化血管变化。在正常卵巢中，巨噬细胞被检测到在黄体和健康和闭锁卵泡的外膜层中。随着巨噬细胞消融的进展，观察到越来越多的卵巢出血，影响黄体和外膜组织，伴随着明显的内皮细胞耗竭、红细胞积累增加和 16 小时时卵泡闭锁增加。这些事件随后发生坏死和严重的结构损伤。这些变化仅限于卵巢，因为 DT 处理不会破坏其他组织的血管，这可能反映了卵巢血管的独特周期性和不同组织中巨噬细胞的异质性。这些结果表明，巨噬细胞在维持卵巢血管完整性方面起着关键作用。
