The impact of ovulation on fallopian tube epithelial cells: evaluating three hypotheses connecting ovulation and serous ovarian cancer.
The impact of ovulation on fallopian tube epithelial cells: evaluating three hypotheses connecting ovulation and serous ovarian cancer.
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DOI：
10.1530/erc-11-0107
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发表时间：
2011-10
影响因子：
3.9
通讯作者：
Burdette JE
中科院分区：
文献类型：
--
作者：
King SM;Hilliard TS;Wu LY;Jaffe RC;Fazleabas AT;Burdette JE
卵巢癌是影响美国妇女的最致命的妇科恶性肿瘤。目前关于卵巢癌病因的假设认为，一生中排卵次数的减少会降低卵巢癌的风险。晚期浆液性癌与输卵管上皮细胞有一些共同的生物标志物，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。在CD1小鼠中，通过溴脱氧尿苷掺入和增殖细胞核抗原染色，与未刺激的小鼠相比，排卵并未增加输卵管上皮细胞的增殖。在超排卵小鼠中，在输卵管中检测到促炎巨噬细胞数量的增加。排卵也增加了phospho-γH2A的水平。X在输卵管上皮细胞中表达，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了输卵管DNA损伤，我们建立了永生化狒狒输卵管上皮细胞系和小鼠输卵管和狒狒输卵管三维器官培养系统。输卵管上皮细胞在体外对促性腺激素或雌二醇的反应中没有增殖或显示增加的DNA损伤。过氧化氢或巨噬细胞条件培养基产生的氧化应激增加了培养的输卵管上皮细胞的DNA损伤。排卵可能通过产生DNA损伤和刺激巨噬细胞浸润影响输卵管上皮，但不通过促性腺激素信号传导增加增殖。
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 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 tubal epithelial cells, 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 tubal epithelial cell line and a three-dimensional organ culture system for mouse oviduct and baboon fallopian tubes were developed. Tubal epithelial cells 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 tubal epithelial cells 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.