Center for Reproductive Sciences, Department of Molecular and Integrative Physiology, Kansas City, KS 66160, USA.
Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Cells. 2022 Mar 24;11(7):1096. doi: 10.3390/cells11071096.
Endometriosis is a significant disease characterized by infertility and pelvic pain in which endometrial stromal and glandular tissue grow in ectopic locations. Altered responsiveness to progesterone is a contributing factor to endometriosis pathophysiology, but the precise mechanisms are poorly understood. Progesterone resistance influences both the eutopic and ectopic (endometriotic lesion) endometrium. An inability of the eutopic endometrium to properly respond to progesterone is believed to contribute to the infertility associated with the disease, while an altered responsiveness of endometriotic lesion tissue may contribute to the survival of the ectopic tissue and associated symptoms. Women with endometriosis express altered levels of several endometrial progesterone target genes which may be due to the abnormal expression and/or function of progesterone receptors and/or chaperone proteins, as well as inflammation, genetics, and epigenetics. MiRNAs are a class of epigenetic modulators proposed to play a role in endometriosis pathophysiology, including the modulation of progesterone signaling. In this paper, we summarize the role of progesterone receptors and progesterone signaling in endometriosis pathophysiology, review miRNAs, which are over-expressed in endometriosis tissues and fluids, and follow this with a discussion on the potential regulation of key progesterone signaling components by these miRNAs, concluding with suggestions for future research endeavors in this area.
子宫内膜异位症是一种以不孕和盆腔疼痛为特征的重大疾病，其中子宫内膜基质和腺体组织在异位部位生长。孕激素反应改变是子宫内膜异位症病理生理学的一个促成因素，但确切的机制尚不清楚。孕激素抵抗影响着在位（子宫内膜）和异位（子宫内膜异位症病灶）的子宫内膜。认为在位子宫内膜不能对孕激素做出适当反应是导致该疾病相关不孕的原因之一，而子宫内膜异位症病灶组织反应性改变可能有助于异位组织的存活和相关症状。子宫内膜异位症患者表达几种子宫内膜孕激素靶基因的改变水平，这可能是由于孕激素受体和/或伴侣蛋白的异常表达和/或功能，以及炎症、遗传和表观遗传。miRNAs 是一类表观遗传调节剂，被认为在子宫内膜异位症病理生理学中发挥作用，包括孕激素信号的调节。在本文中，我们总结了孕激素受体和孕激素信号在子宫内膜异位症病理生理学中的作用，综述了在子宫内膜异位症组织和液中过度表达的 miRNAs，并在此基础上讨论了这些 miRNAs 对关键孕激素信号成分的潜在调节作用，最后对该领域的未来研究工作提出了建议。
