IL-27 promotes decidualization via the STAT3-ESR/PGR regulatory axis

Zhang, Xinyan; Shen, Hui‐Hui; Qin, Xue-Yun; Wang, Chengjie; Hu, Wenting; Liu, Songping; Wu, Jiang‐Nan; Xie, Feng; Xu, Feng-Yuan; Zhao, Shimin; Yuan, Yiyuan; Li, Ming‐Qing

doi:10.1016/j.jri.2022.103623

Cited by 8 publications

(8 citation statements)

References 47 publications

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“…In this study, the level of IL-27 was found to be higher significantly in the stimulated group, which is in agreement with another study that recognized a significant increase in the level of IL-17 and IL-27 in women with unexplained infertility undergo ovulation induction determined instantaneously before ovulation triggering by giving HCG injection if compared with the control fertile women group [17]. As mention in other study that conclude, IL-27 is upregulated by estrogen and progestogen which promotes decidualization possibly through a STAT3-dominant pathway [27]. In other study, there was a relationship between detectable serum IL-1β at the start of an IVF cycle and increasing levels of IL-1β over time and successful IVF outcome [28].…”

Section: Discussionsupporting

confidence: 90%

Interleukin-1β, 27 Level in Stimulated and Non-stimulated PCOS Infertile Women (Cross-Sectional Study)

Al-Obaidi

Thamer

Ibraheem

2022

Open Access Maced J Med Sci

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Background: Polycystic ovary syndrome (PCOS) stands for highly prevalent female endocrine pathology. Females suffering from PCOS have a significantly higher number of inflammatory markers. The IL-1 family members enormously affect the innate immune system. Objectives: Study the changes in the levels of Interleukin- 1ß and Interleukin- 27 in the stimulated and non-stimulated cycle (by gonadotrophin) in polycystic ovarian syndrome women. Methods: Fifty-eight infertile women with polycystic ovary syndrome (PCOS) have been included in this research article. Twenty-nine of them did not undergo ovulation induction (OI) protocols, while the other twenty-nine were under ovulation induction (OI) therapy. Interleukin-1ß and Interleukin -27 measured in both groups, in the stimulated cycle just prior to administration of HCG and on the second day of the menstrual cycle in the non-stimulated females. Results: Both interleukins have been significantly more significant in the ovulation stimulated group than the non-stimulated one, with P-value of (0.04) for Interleukin -1ß and (0.02) for interleukin-27. Conclusion: The ovulation processes involve an increase in the inflammatory process, as demonstrated by the rise in these interleukins' levels. This increase is more prominent in the process of ovulation induction.

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Section: Discussionsupporting

confidence: 90%

Interleukin-1β, 27 Level in Stimulated and Non-stimulated PCOS Infertile Women (Cross-Sectional Study)

Al-Obaidi

Thamer

Ibraheem

2022

Open Access Maced J Med Sci

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“…Our previous work has unraveled that IL-27 could stimulate IL-10 production and facilitate growth and invasion of endometrial stromal cells, contributing to the occurrence and progression of endometriosis [18,19]. We also found that IL-27 could activate decidual COX-2 + M2-like macrophage differentiation, indirectly facilitating decidualization, trophoblast invasion, and maternal-fetal tolerance [20,21]. However, whether IL-27 show effects on bio-functions of trophoblast cells and accounts for FGR development remain unexplained.…”

Section: Introductionmentioning

confidence: 68%

IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction

Zhang¹,

Qin²,

Shen³

et al. 2023

Int. J. Med. Sci.

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Background: Fetal growth restriction (FGR) is characterized by restricted fetal growth and dysregulated placental development. The etiology and pathogenesis still remain elusive. IL-27 shows multiple roles in regulating various biological processes, however, how IL-27 involves in placentation in FGR pregnancy hasn't been demonstrated. Methods: The levels of IL-27 and IL-27RA in FGR and normal placentae were determined by immunohistochemistry, western blot and RT-PCR. HTR-8/SVneo cells and Il27ra -/-murine models have been adopted to evaluate the effects of IL-27 on the bio-functions of trophoblast cells. GO enrichment and GSEA analysis were performed to explore the underlying mechanism. Findings: IL-27 and IL-27RA was lowly expressed in FGR placentae and administration of IL-27 on HTR-8/SVneo could promote its proliferation, migration and invasion. Comparing with wildtypes, Il27ra -/embryos were smaller and lighter, and the placentae from which were poorly developed. In mechanism, the molecules of canonical Wnt/β-catenin pathway (CCND1, CMYC, SOX9) were downregulated in Il27ra -/placentae. In contrast, the expression of SFRP2 (negative regulator of Wnt) was increased. Overexpression of SFRP2 in vitro could impair trophoblast migration and invasion capacity.Interpretation: IL-27/IL-27RA negatively regulates SFRP2 to activate Wnt/β-catenin, and thus promotes migration and invasion of trophoblasts during pregnancy. However, IL-27 deficiency may contribute to the development of FGR by restricting the Wnt activity.

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“…However, in cells transfected with a suppressor of cytokine signaling 3 (SOCS3)-overexpressing plasmid, IL-11 treatment failed to increase p-STAT3 levels, suggesting that SOCS3 overexpression in HESCs diminished IL-11-induced p-STAT3 production and hindered HESC decidualization [24]. Additionally, IL-27 promoted decidualization by upregulating STAT3 phosphorylation in endometrial stromal cells [15]. These findings indicate that STAT3 is a critical regulator of cytokine-related signaling pathways (including IL-6, IL-11, and IL-27), and transcription factors and molecular compounds that modulate decidualization in the uterus (Figure 2).…”

Section: The Function Of Stat3 In Endometrial Stromal Cell Decidualiz...mentioning

confidence: 99%

“…Recent data have indicated that the phosphorylation of STAT3 at Y705 is a crucial regulator of this process. Activation of the STAT3 pathway by members of the IL-6 family of cytokines and other signaling molecules promotes the differentiation of ESCs into decidual cells [13][14][15]. Additionally, STAT3 phosphorylation in the endometrial epithelium determines the success of embryo implantation by regulating uterine receptivity.…”

Section: Introductionmentioning

confidence: 99%

Paradoxical role of phosphorylated STAT3 in normal fertility and the pathogenesis of adenomyosis and endometriosis

Xu,

Wu,

Qin

et al. 2023

Biology of Reproduction

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Signal transducer and activator of transcription 3 (STAT3), when phosphorylated at tyrosine 705, plays an important role in endometrial stromal cell decidualization and the receptivity of the endometrial epithelium during embryo implantation. However, the function of phosphorylated STAT3 (p-STAT3) in normal uterine receptivity is distinct from that in adenomyosis and endometriosis. In normal pregnancy, STAT3 phosphorylation in the endometrial epithelium determines the success of embryo implantation by regulating uterine receptivity. Additionally, p-STAT3 promotes cellular proliferation and differentiation during endometrial decidualization, which is crucial for embryonic development. In contrast, excessive STAT3 phosphorylation occurs in adenomyosis and endometriosis, which may lead to disease progression. Therefore, achieving a delicate balance in STAT3 activation is crucial. This review aimed to focus on the current understanding and knowledge gaps regarding the control of p-STAT3 activity in normal and pathological endometrial processes. This topic is important because precise control of p-STAT3 production could alleviate the symptoms of adenomyosis and endometriosis, improve endometrial receptivity, and potentially mitigate infertility without compromising normal fertility processes.

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IL-27 promotes decidualization via the STAT3-ESR/PGR regulatory axis

Cited by 8 publications

References 47 publications

Interleukin-1β, 27 Level in Stimulated and Non-stimulated PCOS Infertile Women (Cross-Sectional Study)

Interleukin-1β, 27 Level in Stimulated and Non-stimulated PCOS Infertile Women (Cross-Sectional Study)

IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/β-catenin pathway in fetal growth restriction

Paradoxical role of phosphorylated STAT3 in normal fertility and the pathogenesis of adenomyosis and endometriosis

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