Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago College of Pharmacy, 900 S. Ashland, Chicago, Illinois 60612, USA.
Endocr Relat Cancer. 2011 Sep 20;18(5):627-42. doi: 10.1530/ERC-11-0107. Print 2011 Oct.
Ovarian cancer is the most lethal gynecological malignancy affecting American women. Current hypotheses concerning the etiology of ovarian cancer propose that a reduction in the lifetime number of ovulations decreases ovarian cancer risk. Advanced serous carcinoma shares several biomarkers with fallopian tube epithelial cells, suggesting that some forms of ovarian carcinoma may originate in the fallopian tube. Currently, the impact of ovulation on the tubal epithelium is unknown. In CD1 mice, ovulation did not increase tubal epithelial cell (TEC) proliferation as measured by bromodeoxyuridine incorporation and proliferating cell nuclear antigen staining as compared to unstimulated animals. In superovulated mice, an increase in the number of pro-inflammatory macrophages was detected in the oviduct. Ovulation also increased levels of phospho-γH2A.X in TEC, indicating that these cells were susceptible to double-strand DNA breakage following ovulation. To determine which components of ovulation contributed to DNA damage in the fallopian tube, an immortalized baboon TEC cell line and a three-dimensional organ culture system for mouse oviduct and baboon fallopian tubes were developed. TEC did not proliferate or display increased DNA damage in response to the gonadotropins or estradiol alone in vitro. Oxidative stress generated by treatment with hydrogen peroxide or macrophage-conditioned medium increased DNA damage in TEC in culture. Ovulation may impact the fallopian tube epithelium by generating DNA damage and stimulating macrophage infiltration but does not increase proliferation through gonadotropin signaling.
卵巢癌是影响美国女性的最致命妇科恶性肿瘤。目前关于卵巢癌病因的假设提出，一生中排卵次数的减少会降低卵巢癌的风险。高级别浆液性癌与输卵管上皮细胞具有几种共同的生物标志物，这表明某些形式的卵巢癌可能起源于输卵管。目前，排卵对输卵管上皮的影响尚不清楚。与未刺激的动物相比，在 CD1 小鼠中，排卵并没有像溴脱氧尿苷掺入和增殖细胞核抗原染色所测量的那样增加输卵管上皮细胞 (TEC) 的增殖。在超排卵的小鼠中，在输卵管中检测到促炎巨噬细胞数量增加。排卵还增加了 TEC 中磷酸化 γH2A.X 的水平，表明这些细胞在排卵后易受双链 DNA 断裂的影响。为了确定排卵的哪些成分导致输卵管中的 DNA 损伤，开发了一种永生化的狒狒 TEC 细胞系和一种用于小鼠输卵管和狒狒输卵管的三维器官培养系统。TEC 在体外单独对促性腺激素或雌二醇没有增殖或显示增加的 DNA 损伤。用过氧化氢或巨噬细胞条件培养基处理产生的氧化应激增加了培养中的 TEC 的 DNA 损伤。排卵可能通过产生 DNA 损伤和刺激巨噬细胞浸润来影响输卵管上皮，但不会通过促性腺激素信号增加增殖。
