Gonadotropin-induced superovulation drives ovarian surface epithelia proliferation in CD1 mice

Gonadotropin-induced superovulation drives ovarian surface epithelia proliferation in CD1 mice
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DOI:
10.1210/en.2005-1629
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发表时间:
2006-05-01
期刊:
影响因子:
4.8
通讯作者:
Woodruff, TK
Woodruff, TK
中科院分区:
医学2区
文献类型:
--
作者:
Burdette, JE;Kurley, SJ;Woodruff, TK

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卵巢表面上皮(OSE)是一个单层细胞,围绕卵巢,并适应反复撕裂和修复,以应对排卵。OSE细胞被认为是90%卵巢癌的祖细胞。目前,还没有报告OSE对一次排卵事件的增殖总量。在这项研究中,OSE的增殖进行了定量的反应,诱导超排卵的ip注射孕马血清促性腺激素(PMSG)和人绒毛膜促性腺激素(hCG)在未成熟的27天龄的CD 1小鼠使用溴脱氧尿苷(BrdU)。BrdU掺入OSE细胞的时间从hCG注射的时间开始测量,总累积标记为12 h。BrdU掺入也测量从PMSG注射的时间为60小时的总标签的相关增殖与特异性促性腺激素刺激。在所有时间点,超数排卵动物的OSE增殖均显著高于对照小鼠。还在离散解剖切片中分析了增殖,并表明覆盖窦状卵泡和黄体的OSE比卵泡生长远端的OSE增殖更快。最后,评估了排卵引起的细胞凋亡,几乎没有检测到OSE内的细胞死亡。这些数据表明,OSE,特别是靠近窦卵泡和黄体,增殖显着响应促性腺激素PMSG和hCG。因此,卵巢表面细胞对排卵的反应性分裂可能通过增殖诱导的DNA突变和转化细胞进展而导致卵巢癌。
The ovarian surface epithelium (OSE) is a monolayer of cells that surround the ovary and accommodate repeated tear and repair in response to ovulation. OSE cells are thought to be the progenitors of 90% of ovarian cancers. Currently, the total amount of proliferation of the OSE has not been reported in response to one ovulatory event. In this study, proliferation of the OSE was quantified in response to superovulation induced by ip injection of pregnant mare serum gonadotropin ( PMSG) and human chorionic gonadotropin (hCG) in immature 27-d-old CD1 mice using bromodeoxyuridine (BrdU). BrdU incorporation into the OSE cells was measured from the time of hCG injection for a total cumulative label of 12 h. BrdU incorporation was also measured from the time of PMSG injection for a total label of 60 h to correlate proliferation with specific gonadotropin stimulation. The OSE proliferation was significantly higher in superovulated animals compared with control mice at all time points. Proliferation was also analyzed in discrete anatomical sections and indicated that OSE covering antral follicles and corpora lutea proliferated more rapidly than OSE distal to follicular growth. Finally, apoptosis was assessed in response to ovulation, and virtually no cell death within the OSE was detected. These data demonstrate that the OSE, especially near antral follicles and corpora lutea, proliferates significantly in response to the gonadotropins PMSG and hCG. Therefore, ovarian surface cell division in response to ovulation could contribute to ovarian cancer by proliferation-induced DNA mutations and transformed cell progression.