Gene Expression & Human Molecular Genetics Laboratory, Institute of Genetics and Biophysics A.B.T CNR, Naples, Italy.
J Cell Physiol. 2013 Sep;228(9):1927-34. doi: 10.1002/jcp.24358.
Endometriosis is a common benign pathology, characterised by the presence of endometrial tissue outside the endometrial cavity with a prevalence of 10-15% in reproductive-aged women. The pathogenesis is not completely understood, and several theories have been proposed to explain the aetiology. Our group has recently described the presence of ectopic endometrium in a consistent number of human female foetuses analysed by autopsy, reinforcing the hypothesis that endometriosis may be generated by defects during the organogenesis of the female reproductive trait. Herein, in order to identify, at molecular level, changes involved in the disease, we compared the transcriptional profiling of ectopic endometrium with the corresponding eutopic one. Statistical analyses lead us to identify some genes specifically deregulated in the ectopic endometrium, that are involved in gonad developmental process or in wound healing process. Among them, we identified BMP4 and GREM1. BMP4 was never associated before to endometriosis and is involved in the mesoderm-Müllerian duct differentiation. GREM1 is needed for the initial step of the ureter growth and perhaps could possibly be involved in Müller ducts differentiation. These molecules might be related to the endometriosis aetiology since we showed that their expression is not related to the menstrual cycle phase both at RNA and at protein levels. These data support the theory that embryological defects could be responsible of the endometriosis generation.
子宫内膜异位症是一种常见的良性病理，其特征是子宫内膜组织出现在子宫内膜腔外，在育龄妇女中的患病率为 10-15%。其发病机制尚未完全阐明，提出了几种理论来解释其病因。我们的研究小组最近通过尸检描述了在大量人类女性胎儿中存在异位子宫内膜，这进一步支持了子宫内膜异位症可能是由女性生殖器官发生过程中的缺陷引起的假说。在此，为了在分子水平上识别与疾病相关的变化，我们比较了异位和相应的在位子宫内膜的转录谱。统计分析使我们确定了一些在异位子宫内膜中特异性下调的基因，这些基因涉及性腺发育过程或伤口愈合过程。其中，我们鉴定了 BMP4 和 GREM1。BMP4 以前从未与子宫内膜异位症相关，并且参与中胚层-Müller 管分化。GREM1 是输尿管生长的初始步骤所必需的，可能与 Müller 管分化有关。这些分子可能与子宫内膜异位症的发病机制有关，因为我们表明它们的表达在 RNA 和蛋白质水平上都与月经周期阶段无关。这些数据支持胚胎发育缺陷可能是导致子宫内膜异位症发生的理论。
