Cellular and extracellular vaginal changes following murine ovarian removal.
Cellular and extracellular vaginal changes following murine ovarian removal.
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DOI：
10.14814/phy2.15762
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发表时间：
2023-08
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
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由于衰老、盆腔癌治疗、遗传或饮食失调导致的雌激素丧失会影响包括生殖道在内的许多身体系统。具体来说，慢性雌激素分泌不足会导致阴道萎缩、干燥和性交困难等症状。目前的治疗方案，包括阴道雌激素和透明质酸（HA），据说可以改善症状，但纠正机制在很大程度上还没有得到充分研究。为了研究低雌激素阴道环境，特别是细胞外基质（ECM），以及了解当前治疗背后的机制和开发新的治疗方法，我们建立了一个可靠且可重复的动物模型。对9周龄CD1小鼠进行双侧卵巢切除术（OVX）。由于卵巢切除导致雌激素减少1个月后，与假手术对照组相比，小鼠在雌激素减少状态下的表型与人类阴道组织相似。与假手术小鼠相比，OVX小鼠的子宫体重比降低了80%，阴道上皮明显变薄。雌激素信号在OVX中发生改变，但粘膜下ERα定位无统计学差异。OVX小鼠粘膜下HA定位改变，CD44表达降低。OVX后胶原蛋白翻转发生改变。炎症谱也被破坏，OVX小鼠粘膜下阴道CD45+和F4/80+细胞群显著减少。这些结果表明，由于雌激素水平降低，细胞和分子的变化发生了改变。开发新的治疗方法，以减少雌激素阴道症状依赖于更好地了解不仅是细胞的变化，而且改变阴道ECM环境。使用这种小鼠模型的进一步研究有可能推进女性阴道健康治疗，并有助于理解健康、衰老和患病状态下器官系统之间的相互作用。小鼠卵巢切除术导致循环雌激素减少，子宫：体重比减小。低雌激素阴道状态显示改变雌激素信号，透明质定位，胶原蛋白翻转和炎症谱。
Loss of estrogen as a result of aging, pelvic cancer therapy, genetics, or eating disorders affects numerous body systems including the reproductive tract. Specifically, a chronic hypoestrogenic state fosters debilitating vaginal symptoms like atrophy, dryness, and dyspareunia. Current treatment options, including vaginal estrogen and hyaluronan (HA), anecdotally improve symptoms, but rectifying mechanisms are largely understudied. In order to study the hypoestrogenic vaginal environment, in particular the extracellular matrix (ECM), as well as understand the mechanisms behind current treatments and develop new therapies, we characterized a reliable and reproducible animal model. Bilateral ovariectomies (OVX) were performed on 9‐week‐old CD1 mice. After 1 month of estrogen loss due to ovarian removal, a phenotype that is similar to human vaginal tissue in an estrogen reduced state was noted in mice compared to sham‐operated controls. The uterine to body weight ratio decreased by 80% and vaginal epithelium was significantly thinner in OVX compared to sham mice. Estrogen signaling was altered in OVX, but submucosal ERα localization did not reach statistical differences. HA localization in the submucosal area was altered and CD44 expression decreased in OVX mice. Collagen turn‐over was altered following OVX. The inflammation profile was also disrupted, and submucosal vaginal CD45+ and F4/80+ cell populations were significantly reduced in the OVX mice. These results show altered cellular and molecular changes due to reduced estrogen levels. Developing new treatments for hypoestrogenic vaginal symptoms rely on better understanding of not only the cellular changes, but also the altered vaginal ECM environment. Further studies using this mouse model has the potential to advance women's vaginal health treatments and aid in understanding the interplay between organ systems in both healthy, aged, and diseased states. Murine ovariectomy resulted in decreased circulating estrogen as evidence by smaller uterine: BW ratio. The hypoestrogenic vaginal state displayed altered estrogen signaling, hyaluron localization, collagen turn over, and inflammatory profile.
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影响因子：
5.3
作者：
Ceccarelli S;D'Amici S;Vescarelli E;Coluccio P;Matricardi P;di Gioia C;Benedetti Panici P;Romano F;Frati L;Angeloni A;Marchese C
通讯作者：
Marchese C
影响因子：
6.7
作者：
Chen, GD;Oliver, RH;Yeh, O
通讯作者：
Yeh, O
影响因子：
4.8
作者：
Couse, JF;Lindzey, J;Korach, KS
通讯作者：
Korach, KS
影响因子：
4
作者：
Dusio, Giuseppina F.;Cardani, Diego;Rumio, Cristiano
通讯作者：
Rumio, Cristiano
影响因子：
4.8
作者：
Buckanan, DL;Kurita, T;Cooke, PS
通讯作者：
Cooke, PS