PI3K/AKT pathway is altered in the endometriosis patient’s endometrium and presents differences according to severity stage

Abstract

Based on the inflammatory nature and hormone-dependency of endometriosis, PI3K/AKT signaling appears to influence its progression. Could the endometriosis stages be linked to differential changes in PI3K/AKT pathway regulation? The objective is to evaluate the expression of PI3K, PTEN, AKT and p-AKT in endometrial human biopsies, according to the presence or absence of the disease, and to assess the underlying differences regarding the endometriosis stages. Biopsy specimens of the ectopic and eutopic endometrium were obtained from twenty women with untreated peritoneal endometriosis as well as endometrium biopsies from nine controls. Our study revealed an increased expression of PI3K in eutopic and ectopic endometrium from patients with endometriosis, and a reduced expression of PTEN and increased levels of AKT phosphorylation, compared to control endometrium. Both eutopic and ectopic endometrium from patients with minimal-mild endometriosis expressed a significant reduced PTEN level compared to the respective endometrium from patients with moderate-severe endometriosis. The ratio p-AKT/total AKT showed higher levels of AKT phosphorylation in endometriotic tissue from patients with minimal-mild endometriosis. This study has firmly confirmed the alteration in PI3K/AKT pathway regulation and demonstrated clear differences between the stages of endometriosis, emphasizing the importance of this pathway in the first stage of the disease.

基于子宫内膜异位症的炎症性质和激素依赖性, PI3K/AKT信号可能影响其进展。子宫内膜异位症的分期是否与PI3K/AKT通路调节的不同变化有关？本研究目的是根据是否存在子宫内膜异位症, 评估PI3K、PTEN、AKT和p-AKT在子宫内膜活检中的表达, 并评估其子宫内膜异位症分期的潜在差异。对20例未经治疗的腹膜子宫内膜异位症患者的异位和在位子宫内膜进行了活检, 并对9例对照者进行了子宫内膜活检。我们的研究显示, 与对照组相比, 子宫内膜异位症患者在位和异位内膜中PI3K的表达增加, PTEN的表达减少, AKT磷酸化水平升高。轻度子宫内膜异位症患者的在位子宫内膜和异位子宫内膜与中重度子宫内膜异位症患者的相应子宫内膜相比, PTEN水平显著降低, p-AKT/AKT比值显示轻度子宫内膜异位症患者子宫内膜异位组织中AKT磷酸化水平较高。本研究证实了PI3K/AKT通路调节的改变, 并显示了子宫内膜异位症各阶段之间的明显差异, 强调了该通路在疾病第一阶段的重要性。