Ovarian surface epitheliectomy in the non-human primate: continued cyclic ovarian function and limited epithelial replacement
Ovarian surface epitheliectomy in the non-human primate: continued cyclic ovarian function and limited epithelial replacement
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DOI：
10.1093/humrep/der061
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发表时间：
2011-06-01
影响因子：
6.1
通讯作者：
Stouffer, Richard L.
中科院分区：
文献类型：
--
作者：
Wright, Jay W.;Pejovic, Tanja;Stouffer, Richard L.
背景资料：女性癌症死亡的第五大原因是卵巢癌（OC），它主要起源于卵巢周围的卵巢表面上皮（OSE）。永久性切除OSE可以提供一种新的策略，大大降低OC的风险，同时保留卵巢功能的好处，包括配子和类固醇生成。必须确定卵巢表面上皮切除术（OSEx）是否会产生有害的副作用，包括月经周期的丧失，不孕或疤痕（e。G.粘连），在该策略的任何临床应用之前。为了实现这一目标，我们选择了非人类灵长类动物，恒河猴，长期（12个月）的OSEx.Methods的影响研究：恒河猴女性进行OSEx洗涤剂治疗，然后监测月经周期（月经，类固醇生成和卵泡发育）和不良副作用（组织瘢痕或粘连）。在6个月或12个月时收集卵巢，并检查组织损伤、卵泡破裂和黄体退化的证据。卵巢表面的上皮替代的迹象进行了免疫组织学检查，使用标记OSE和菌毛上皮（FE），一个可能的替代来源的盆腔肿瘤诊断为OC。结果：OSEx后，月经周期长度，雌激素和孕激素的生产，卵泡破裂和黄体退化出现正常。未观察到粘连证据。在OSEx后6个月和12个月，卵巢表面表达OSE和FE标志物的细胞稀疏。在这个人群中的生殖活性显着low.Conclusions：OSEx可以提供一种新的方法来降低OC的风险，而不牺牲卵巢功能，虽然对生育能力的影响仍有待测试。通过增强增殖的上皮替代的缺乏表明OSEx不会增加恶性潜能。完整和永久的OSEx可能是可行的。
Background: The fifth leading cause of cancer deaths among women is ovarian cancer (OC), which originates primarily in the ovarian surface epithelium (OSE) that surrounds the ovary. Permanent removal of the OSE could provide a novel strategy to substantially reduce OC risk, while retaining the benefits of ovarian function, including gameto- and steroidogenesis. It must be determined whether ovarian surface epitheliectomy (OSEx) carries deleterious side effects, including loss of menstrual cyclicity, infertility or scarring (e. g. adhesions), prior to any clinical application of this strategy. To achieve this, we selected the non-human primate, rhesus macaque, for long-term (12 month) studies on the effects of OSEx.Methods: Rhesus macaque females underwent OSEx by detergent treatment and were then monitored for menstrual cyclicity (menstruation, steroidogenesis and follicle development) and adverse side effects (tissue scarring or adhesions). Ovaries were collected at 6 or 12 months and examined for evidence of tissue damage, follicle rupture and regression of the corpus luteum. The ovarian surface was examined immunohistologically for signs of epithelial replacement, using markers for OSE and fimbrial epithelium (FE), a possible alternative source of pelvic tumors diagnosed as OC.Results: After OSEx, menstrual cycle length, estrogen and progesterone production, follicle rupture and luteal regression appeared normal. No evidence of adhesions was seen. At 6 and 12 months post-OSEx, the ovarian surface was sparsely populated by cells expressing OSE and FE markers. Proliferative activity in this population was notably low.Conclusions: OSEx may provide a novel method to reduce the risk of OC, without sacrificing ovarian function, although the effects on fertility remain to be tested. The absence of epithelial replacement via enhanced proliferation suggests OSEx does not increase malignant potential. Complete and permanent OSEx may be feasible.