An Observation of the Role of Autophagy in Patients with Endometriosis of Different Stages during Secretory Phase and Proliferative Phase

Li M, Meng Li, Lu MS, Mei-Song Lu, Meisong Lu, Mei-Ling Liu, Liu ML, Meiling Liu, Suo Deng, Deng S, Xiao‐Han Tang, Tang XH, Xiao-Han Tang, Han C, Cui Han, Hongli Wang, Wang HL, Hong-Li Wang, Li PL, Peiling Li, Pei-Ling Li
Current gene therapy · 2018 · vol. 18(5) , pp. 286–295 · doi:10.2174/1566523218666181008155039 · PMID:30306868 · W2895871613
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Autophagic activity, indicated by LC3B-II and P62 levels, was decreased in ectopic endometriosis tissue, particularly in later stages during the secretory phase, suggesting a role in disease pathogenesis.

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This study investigated autophagic activity in endometrial tissues from 73 women, comparing healthy controls with patients at different stages of endometriosis across proliferative and secretory menstrual phases. Researchers measured the expression levels of LC3B-II and P62 proteins to assess autophagy, finding that while healthy tissue showed phase-dependent changes, endometriotic lesions exhibited significantly lower LC3B-II and higher P62 levels compared to eutopic tissue. The data indicated that decreased autophagy in ectopic endometrium was particularly pronounced in advanced disease stages during the secretory phase, suggesting a link between lost periodicity and disease progression. This paper is centrally about endometriosis — specifically examining how altered autophagy markers correlate with lesion severity and menstrual cycle phases in endometriotic tissue.

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Abstract

BACKGROUND: Autophagy exists widely in various physiological and pathological conditions. Lots of investigations have verified that the autophagic activity is always related to the occurrence and the development of cancer. Endometriosis (EMs) is a disease that endometrium-like tissues abnormally grow outside the uterus and also considered to possess the characters of tumor because of its malignant biological behavior. INTRODUCTION: Recently, several studies have already revealed that autophagy may play a potential role in proliferative-phase EMs. However, the function of autophagic activity in secretory-phase EMs is still unclear. METHODS: In our work, we explored autophagic activity between normal endometrium and EMs lesion endometrium during different menstrual phases and EMs stages. The clinical endometrium samples from 73 women were selected in this study, including 30 healthy individuals and 43 patients with EMs (endometrium samples include eutopic and its matched ectopic endometrium). All the participants were divided into two groups according to the menstrual cycle, namely proliferative-phase and secretive- phase group. Among the patients with EMs, 22 individuals in proliferative phase and the other 21 individuals in secretory phase were further classified into the groups of Stage I-II and Stage III-IV according to revised-American Fertility Society (r-AFS). Two autophagy-related proteins microtubuleassociated protein 1 light chain 3 beta-II (LC3B-II) and sequestosome protein (P62), which are believed to be the indicators of autophagy activity, were chosen in the study. Immunohistochemical (IHC) staining, Western blot assay and Real-Time quantitative Polymerase Chain Reaction (RTqPCR) were used to examine the expression of LC3B-II and P62 in protein and mRNA level accordingly. RESULT: It showed that the expression of LC3B-II both in protein and mRNA level decreased and that of P62 increased in secretory phase of the healthy group (P0.05). In addition, the expression of LC3B-II in ectopic endometrium group was significantly lower than that of its eutopic endometrium group (P<0.05), and the expression of P62 was significantly higher accordingly (P0.05). Furthermore, compared to Stage I-II EMs group, the expression of LC3B-II was significantly lower (P<0.05) and P62 was significantly higher (P<0.05) in Stage III-IV EMs during secretory phase. CONCLUSION: Taken together, the periodicity-losing in EMs and the decreased autophagic activity in ectopic endometrium may exert a potential role in the pathogenesis of EMs. Down-regulated autophagy of ectopic endometrium in secretory phase may be related to the progression of EMs.
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Abstract

Introduction: Recently, several studies have already revealed that autophagy may play a potential role in proliferative-phase EMs. However, the function of autophagic activity in secretory-phase EMs is still unclear.

Methods

In our work, we explored autophagic activity between normal endometrium and EMs lesion endometrium during different menstrual phases and EMs stages. The clinical endometrium samples from 73 women were selected in this study, including 30 healthy individuals and 43 patients with EMs (endometrium samples include eutopic and its matched ectopic endometrium). All the participants were divided into two groups according to the menstrual cycle, namely proliferative-phase and secretive- phase group. Among the patients with EMs, 22 individuals in proliferative phase and the other 21 individuals in secretory phase were further classified into the groups of Stage I-II and Stage III-IV according to revised-American Fertility Society (r-AFS). Two autophagy-related proteins microtubuleassociated protein 1 light chain 3 beta-II (LC3B-II) and sequestosome protein (P62), which are believed to be the indicators of autophagy activity, were chosen in the study. Immunohistochemical (IHC) staining, Western blot assay and Real-Time quantitative Polymerase Chain Reaction (RTqPCR) were used to examine the expression of LC3B-II and P62 in protein and mRNA level accordingly.

Result

It showed that the expression of LC3B-II both in protein and mRNA level decreased and that of P62 increased in secretory phase of the healthy group (P0.05). In addition, the expression of LC3B-II in ectopic endometrium group was significantly lower than that of its eutopic endometrium group (P<0.05), and the expression of P62 was significantly higher accordingly (P0.05). Furthermore, compared to Stage I-II EMs group, the expression of LC3B-II was significantly lower (P<0.05) and P62 was significantly higher (P<0.05) in Stage III-IV EMs during secretory phase.

Conclusion

Taken together, the periodicity-losing in EMs and the decreased autophagic activity in ectopic endometrium may exert a potential role in the pathogenesis of EMs. Down-regulated autophagy of ectopic endometrium in secretory phase may be related to the progression of EMs.

Keywords

Autophagy, Endometriosis, LC3B-II, P62, Proliferative and secretory phase, IHC.

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Condition tags

endometriosis

MeSH descriptors

Autophagy Autophagy-Related Proteins Endometriosis Endometrium Adult Autophagy Autophagy-Related Proteins Autophagy-Related Proteins Disease Progression Endometriosis Endometriosis Endometriosis Endometrium Female Gene Expression Humans Menstrual Cycle Microtubule-Associated Proteins Microtubule-Associated Proteins Microtubule-Associated Proteins

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