Impaired decidualization of human endometrial stromal cells from women with adenomyosis†

Peng, Yaoming; Jin, Zhixing; Liu, Haiou; Xu, Congjian

doi:10.1093/biolre/ioab017

Cited by 19 publications

(9 citation statements)

References 45 publications

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“…The expression of candidate biomarkers associated with the decidualization process was significantly downregulated in the eutopic endometria of patients with adenomyosis compared to the normal endometria of control women [ 51 ]. The process was often accompanied by an abnormal increase in endometrial cell proliferation [ 4 ]. Reduced expression of these candidate markers causes decidualization failure [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

“…Increased estrogen biosynthesis and progesterone resistance have been reported to exert many regulatory functions, including endometrial quality and quantity control [ 3 ]. Progesterone resistance is associated with loss of normal endometrial functions (e.g., hemostasis and successful pregnancy), leading to heavy menstrual bleeding, impaired decidualization, nonreceptive endometrial state, and disease establishment and progression [ 3 , 4 ]. Adenomyosis is a multistep disease caused by the accumulation of epigenetic alterations and genetic mutations, dysfunction of decidualization, the promotion of tissue injury caused at the endometrial–myometrial interface, altered expression of angiogenesis-related molecules, the acquisition of invasive traits, and the progression of pathological tissue remodeling in the myometrium [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Kobayashi

2023

IJERPH

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Adenomyosis is an estrogen-dependent gynecologic disease characterized by the myometrial invasion of the endometrial tissue. This review summarized the current understanding and recent findings on the pathophysiology of adenomyosis, focusing on repeated menstruation, persistent inflammation, and impaired spontaneous decidualization. A literature search was performed in the PubMed and Google Scholar databases from inception to 30 April 2022. Thirty-one full-text articles met the eligibility criteria. Repeated episodes of physiological events (i.e., endometrial shedding, damage, proliferation, differentiation, repair, and regeneration) during the menstrual cycle are associated with inflammation, angiogenesis, and immune processes. The decidualization process in humans is driven by the rise in progesterone levels, independently of pregnancy (i.e., spontaneous decidualization). Adenomyotic cells produce angiogenic and fibrogenic factors with the downregulation of decidualization-associated molecules. This decidualization dysfunction and persistent inflammation are closely related to the pathogenesis of adenomyosis. Recently, it has been found that the reproductive tract microbiota composition and function in women with adenomyosis differ from those without. An increase in opportunistic pathogens and a decrease in beneficial commensals may promote impaired defense mechanisms against inflammation and predispose women to uncontrolled endometrial inflammation. However, currently, there is no direct evidence that adenomyosis is linked to pre-existing inflammation and impaired spontaneous decidualization. Overall, persistent inflammation, impaired spontaneous decidualization, and microbiota dysbiosis (i.e., an imbalance in the composition and function of endometrial microbiota) may be involved in the pathophysiology of adenomyosis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Kobayashi

2023

IJERPH

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“…The CCAAT/enhancer binding protein CEBPB belongs to a family of leucine-zipper TFs that participate in physiological processes such as energy metabolism, cell proliferation, and differentiation ( Huang et al, 2020 ). CEBPB was shown to be related to impaired decidualization of human endometrial stromal cells ( Peng et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single-Cell RNA Sequencing

Zhou

Wang

Yang

et al. 2022

Molecules and Cells

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Trophoblasts, important functional cells in the placenta, play a critical role in maintaining placental function. The heterogeneity of trophoblasts has been reported, but little is known about the trophoblast subtypes and distinctive functions during preeclampsia (PE). In this study, we aimed to gain insight into the cell type-specific transcriptomic changes by performing unbiased single-cell RNA sequencing (scRNA-seq) of placental tissue samples, including those of patients diagnosed with PE and matched healthy controls. A total of 29,006 cells were identified in 11 cell types, including trophoblasts and immune cells, and the functions of the trophoblast subtypes in the PE group and the control group were also analyzed. As an important trophoblast subtype, extravillous trophoblasts (EVTs) were further divided into 4 subgroups, and their functions were preliminarily analyzed. We found that some biological processes related to pregnancy, hormone secretion and immunity changed in the PE group. We also identified and analyzed the regulatory network of transcription factors (TFs) identified in the EVTs, among which 3 modules were decreased in the PE group. Then, through in vitro cell experiments, we found that in one of the modules, CEBPB and GTF2B may be involved in EVT dysfunction in PE. In conclusion, our study showed the different transcriptional profiles and regulatory modules in trophoblasts between placentas in the control and PE groups at the single-cell level; these changes may be involved in the pathological process of PE, providing a new molecular theoretical basis for preeclamptic trophoblast dysfunction.

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“…IL-17 stimulates endometrial stromal cells to secrete IL-8 ( 80 ), which promotes the proliferation and survival of endometrial cells and acts on the chemoattraction and activation of neutrophils ( 81 , 82 ). However, when excessively elevated in endometrial stromal cells, IL-8 impairs their ability to decidualize, leading to a non-receptive endometrium ( 83 ).…”

Section: Ilc3smentioning

confidence: 99%

Emerging Concepts in Innate Lymphoid Cells, Memory, and Reproduction

et al. 2022

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Members of the innate immune system, innate lymphoid cells (ILCs), encompass five major populations (Natural Killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells) whose functions include defense against pathogens, surveillance of tumorigenesis, and regulation of tissue homeostasis and remodeling. ILCs are present in the uterine environment of humans and mice and are dynamically regulated during the reproductive cycle and pregnancy. These cells have been repurposed to support pregnancy promoting maternal immune tolerance and placental development. To accomplish their tasks, immune cells employ several cellular and molecular mechanisms. They have the capacity to remember a previously encountered antigen and mount a more effective response to succeeding events. Memory responses are not an exclusive feature of the adaptive immune system, but also occur in innate immune cells. Innate immune memory has already been demonstrated in monocytes/macrophages, neutrophils, dendritic cells, and ILCs. A population of decidual NK cells characterized by elevated expression of NKG2C and LILRB1 as well as a distinctive transcriptional and epigenetic profile was found to expand during subsequent pregnancies in humans. These cells secrete high amounts of interferon-γ and vascular endothelial growth factor likely favoring placentation. Similarly, uterine ILC1s in mice upregulate CXCR6 and expand in second pregnancies. These data provide evidence on the development of immunological memory of pregnancy. In this article, the characteristics, functions, and localization of ILCs are reviewed, emphasizing available data on the uterine environment. Following, the concept of innate immune memory and its mechanisms, which include epigenetic changes and metabolic rewiring, are presented. Finally, the emerging role of innate immune memory on reproduction is discussed. Advances in the comprehension of ILC functions and innate immune memory may contribute to uncovering the immunological mechanisms underlying female fertility/infertility, placental development, and distinct outcomes in second pregnancies related to higher birth weight and lower incidence of complications.

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Impaired decidualization of human endometrial stromal cells from women with adenomyosis†

Cited by 19 publications

References 45 publications

Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Endometrial Inflammation and Impaired Spontaneous Decidualization: Insights into the Pathogenesis of Adenomyosis

Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single-Cell RNA Sequencing

Emerging Concepts in Innate Lymphoid Cells, Memory, and Reproduction

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