Kaitu'u-Lino Tu'uhevaha J, Phillips David J, Morison Naomi B, Salamonsen Lois A
Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia.
Endocrinology. 2009 Apr;150(4):1904-11. doi: 10.1210/en.2008-0738. Epub 2008 Nov 20.
Abnormal uterine bleeding can severely affect the quality of life for women. After menstruation, the endometrium must adequately repair to limit and stop bleeding. Abnormal uterine bleeding may result from incorrect or inadequate endometrial repair after menstruation. Previous studies have shown an important contribution of activin to skin wound healing, with severely delayed wound repair observed in animals transgenically induced to overexpress activin's natural inhibitor, follistatin. Activin subunits have also been identified within human endometrium; however, their role in endometrial repair is unknown. We assessed the contribution of activin to endometrial repair after menses using a human in vitro cell wounding method and our well-characterized mouse model of endometrial breakdown and repair applied to mice overexpressing follistatin. Endometrial repair after menses is initiated with reepithelialization of the uterine surface. To mimic this repair, we utilized a human endometrial epithelial cell line (ECC-1) and demonstrated significant stimulation of wound closure after activin A administration, and attenuation of this response by addition of follistatin. Immunolocalization of activin subunits, betaA and betaB, in control endometrium from the mouse model demonstrated specific epithelial and stromal localization and some leukocyte staining (betaA) around sites of endometrial repair, suggestive of a role for activin in this process. Follistatin-overexpressing animals had significantly higher circulating follistatin levels than wild-type littermates. There was a significant delay in endometrial repair after breakdown in follistatin transgenic animals compared with control animals. This study demonstrates for the first time a functional role for activin in endometrial repair after menses.
异常子宫出血会严重影响女性的生活质量。月经结束后，子宫内膜必须充分修复以限制并停止出血。异常子宫出血可能是由于月经后子宫内膜修复不正确或不充分所致。先前的研究表明，激活素对皮肤伤口愈合有重要作用，在转基因诱导过度表达激活素天然抑制剂卵泡抑素的动物中，观察到伤口修复严重延迟。激活素亚基也已在人类子宫内膜中被鉴定出来；然而，它们在子宫内膜修复中的作用尚不清楚。我们使用人类体外细胞损伤方法以及我们建立的、特征明确的小鼠子宫内膜崩解和修复模型（应用于过表达卵泡抑素的小鼠），评估了激活素在月经后子宫内膜修复中的作用。月经后子宫内膜的修复始于子宫表面的重新上皮化。为模拟这种修复过程，我们利用了一种人类子宫内膜上皮细胞系（ECC-1），并证明给予激活素A后伤口闭合受到显著刺激，而添加卵泡抑素会减弱这种反应。在小鼠模型的对照子宫内膜中，激活素亚基βA和βB的免疫定位显示，在子宫内膜修复部位周围有特定的上皮和基质定位以及一些白细胞染色（βA），提示激活素在这一过程中发挥作用。过表达卵泡抑素的动物循环卵泡抑素水平明显高于野生型同窝仔。与对照动物相比，卵泡抑素转基因动物在子宫内膜崩解后的修复明显延迟。这项研究首次证明了激活素在月经后子宫内膜修复中的功能作用。
