MRC Centre for Reproductive Health, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
Hum Reprod Update. 2017 Sep 1;23(5):548-559. doi: 10.1093/humupd/dmx016.
Endometriosis is estimated to affect 6-10% of women of reproductive age and it is associated with chronic pelvic pain, dysmenorrhoea and subfertility. It is currently managed surgically or medically but symptoms recur in up to 75% of cases and available medical treatments have undesirable side effects. Endometriosis is defined as the presence of endometrial tissue outside the uterus with lesions typically found on the peritoneum. The aetiology of endometriosis is uncertain but there is increasing evidence that transforming growth factor (TGF)-β plays a major role.
A descriptive review was undertaken of the published literature on the expression pattern of TGF-β ligands and signalling molecules in women with and without endometriosis, and on the potential roles of TGF-β signalling in the development and progression of peritoneal endometriosis. The current understanding of the TGF-β signalling pathway is summarized.
We searched the Pubmed database using the terms 'transforming growth factor beta' and 'endometriosis' for studies published between 1995 and 2016. The initial search identified 99 studies and these were used as the basic material for this review. We also extended our remit for important older publications. In addition, we searched the reference lists of studies used in this review for additional studies we judged as relevant. Studies which were included in the review focused on peritoneal endometriosis only as increasing evidence suggests that ovarian and deep endometriosis may have a differing pathophysiology. Thus, a final 95 studies were included in the review.
TGF-β1 is reported to be increased in the peritoneal fluid, serum, ectopic endometrium and peritoneum of women with endometriosis compared to women without endometriosis, and TGF-β1-null mice have reduced endometriosis lesion growth when compared to their wild-type controls. Studies in mice and women have indicated that increasing levels of TGF-β ligands are associated with decreased immune cell activity within the peritoneum, together with an increase in ectopic endometrial cell survival, attachment, invasion and proliferation, during endometriosis lesion development. TGF-β1 has been associated with changes in ectopic endometrial and peritoneal cell metabolism and the initiation of neoangiogenesis, further fuelling endometriosis lesion development.
Together these studies suggest that TGF-β1 plays a major role in the development of peritoneal endometriosis lesions and that targeting this pathway may be of therapeutic potential.
子宫内膜异位症估计影响 6-10%的育龄妇女，与慢性盆腔疼痛、痛经和不孕有关。目前通过手术或药物治疗，但高达 75%的病例症状复发，并且现有的药物治疗存在不良副作用。子宫内膜异位症被定义为子宫内膜组织出现在子宫外，病变通常位于腹膜上。子宫内膜异位症的病因尚不确定，但越来越多的证据表明转化生长因子 (TGF)-β 发挥主要作用。
对已发表的关于有和没有子宫内膜异位症的妇女中 TGF-β 配体和信号分子表达模式的文献进行描述性综述，并对 TGF-β 信号在腹膜子宫内膜异位症发展和进展中的潜在作用进行综述。总结目前对 TGF-β 信号通路的理解。
我们使用术语“转化生长因子β”和“子宫内膜异位症”在 Pubmed 数据库中进行搜索，以检索 1995 年至 2016 年期间发表的研究。初步搜索确定了 99 项研究，这些研究被用作本综述的基础材料。我们还扩展了对重要的旧出版物的范围。此外，我们还搜索了本综述中使用的研究的参考文献列表，以获取我们认为相关的其他研究。被纳入本综述的研究仅关注腹膜子宫内膜异位症，因为越来越多的证据表明卵巢和深部子宫内膜异位症可能具有不同的病理生理学。因此，最终有 95 项研究被纳入综述。
与没有子宫内膜异位症的妇女相比，子宫内膜异位症妇女的腹膜液、血清、异位子宫内膜和腹膜中 TGF-β1 报告增加，并且与野生型对照相比，TGF-β1 缺失小鼠的子宫内膜异位症病变生长减少。在小鼠和妇女中的研究表明，TGF-β 配体水平升高与腹膜内免疫细胞活性降低以及异位子宫内膜细胞存活、附着、侵袭和增殖增加有关，在子宫内膜异位症病变发展过程中。TGF-β1 与异位子宫内膜和腹膜细胞代谢的变化以及新血管生成的启动有关，进一步促进了子宫内膜异位症病变的发展。
这些研究表明，TGF-β1 在腹膜子宫内膜异位症病变的发展中起主要作用，靶向该途径可能具有治疗潜力。
