The development of a mouse model of ovarian endosalpingiosis
The development of a mouse model of ovarian endosalpingiosis
复制标题
DOI：
10.1210/en.2005-0697
复制
发表时间：
2005-12-01
期刊：
影响因子：
4.8
通讯作者：
Woodruff, TK
中科院分区：
文献类型：
--
作者：
Bristol-Gould, SK;Hutten, CG;Woodruff, TK
盆腔疼痛是女性常见的症状，通常与排卵、子宫内膜异位症、早孕、卵巢癌和囊肿有关。对这些不同病因引起的每一种疾病进行明确的鉴别诊断是困难的，并且可能会减慢治疗的速度，而在卵巢癌的情况下，治疗可能是致命的。卵巢输卵管内肿大是一种盆腔疾病，其典型特征是存在由良性输卵管/输卵管上皮排列的囊性腺结构，也与女性盆腔疼痛有关。这些上皮囊性结构的确切细胞前体尚不清楚，也没有已知的与卵巢癌的联系。通过使用缪勒氏抑制物质启动子（MIS-Smad2-dn）将tgf - β转录因子Smad2的显性阴性版本引导到卵巢，建立了卵巢输卵管内膜增生的小鼠模型。雌性小鼠早在3个月大时就出现卵巢输卵管内表型。重要的是，囊肿连续卵巢表面上皮已被确定，表明这些囊肿细胞可能来源于高度可塑性的卵巢表面上皮细胞层。导致激活素作用丧失的第二种转基因小鼠模型（抑制素α亚基转基因小鼠）产生类似的囊性结构，支持该疾病发病时对tgf - β /激活素/Smad2的依赖。
Pelvic pain is a common presenting ailment in women often linked to ovulation, endometriosis, early pregnancy, ovarian cancer, and cysts. Clear differential diagnosis for each condition caused by these varied etiologies is difficult and may slow the delivery of therapy that, in the case of ovarian cancer, could be fatal. Ovarian endosalpingiosis, a pelvic condition typified by the presence of cystic glandular structures lined by benign tubal/salpingeal epithelium, is also associated with pelvic pain in women. The exact cellular antecedents of these epithelial lined cystic structures are not known, nor is there a known link to ovarian cancer. A mouse model of ovarian endosalpingiosis has been developed by directing a dominant-negative version of the TGF-beta transcription factor, Smad2, to the ovary using the Mullerian-inhibiting substance promoter (MIS-Smad2-dn). Female mice develop an ovarian endosalpingeal phenotype as early as 3 months of age. Importantly, cysts continuous with the ovarian surface epithelial have been identified, indicating that these cyst cells may be derived from the highly plastic ovarian surface epithelial cell layer. A second transgenic mouse model that causes loss of activin action (inhibin alpha-subunit transgenic mice) develops similar cystic structures, supporting a TGF-beta/activin/Smad2 dependence in the onset of this disease.