Increased peritoneal and endometrial gene expression of biologically relevant cytokines and growth factors during the menstrual phase in women with endometriosis

Kyama, Cleophas; Overbergh, Lutgart; Debrock, Sophie; Valckx, Dirk; Perre, Sarah Vander; Meuleman, Christel; Mihályi, Attila; Mwenda, Jason M.; Mathieu, Chantal; D’Hooghe, Thomas

doi:10.1016/j.fertnstert.2005.11.060

Cited by 128 publications

(94 citation statements)

References 25 publications

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“…This is a proinflammatory disease, with an increased peritoneal fluid volume that contains increased concentrations of white blood cells and activated peritoneal macrophages, which together with endometriotic lesions and macroscopically normal peritoneum are significant contributors to IL6 production and also other inflammatory and invasive molecules mediated by local NFKB activation (Hastings & Fazleabas 2006, Kyama et al 2006, Ulukus et al 2006, Lousse et al 2008, Montagna et al 2008. In the present study, IL6 was exclusively analysed in ex vivo eutopic endometrium, making a difference from those reports using ectopic endometrium or stromal cell cultures in which the paracrine communication of cell compartment was lost.…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

Ponce¹,

Torres²,

Galleguillos³

et al. 2009

Reproduction

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In order to investigate the role of the nuclear factor kB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IkB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysed RELA, CHUK, NFKBIA and IL6 mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P!0.05) in NFKBIA mRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P!0.05) in IL6 mRNA and protein (61%), NFKBIA mRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.

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Section: Discussionmentioning

confidence: 99%

Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

Ponce¹,

Torres²,

Galleguillos³

et al. 2009

Reproduction

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“…7 Deficiencies in the in vitro embryo culture environment, as well as the gonadotrophin-induced altered hormone environment imposed on the oocyte and the tract prior to conception, predispose to growth restriction and attendant life-long effects on children. 7,71,72 In part, these effects are likely to be mediated by the altered cytokine environment accompanying each of these states, with potentially elevated inflammatory cytokines in PCOS 73 and endometriosis, 74 dysregulated cytokine synthesis after ovarian hyperstimulation 75 and absence of female tract cytokines from IVF embryo culture. These would be expected to be aggravated by maternal insulin resistance and obesity, where chronic inflammation is induced by fatty acids and enteric LPS which act as ligands for TLR4 to induce inflammatory cytokines in peripheral tissues.…”

Section: Significance For Infertility Ivf Treatment and Pathologies mentioning

confidence: 99%

Peri‐Conceptual Cytokines – Setting the Trajectory for Embryo Implantation, Pregnancy and Beyond

Robertson

Chin

Glynn

et al. 2011

American J Rep Immunol

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Citation Robertson SA, Chin PY, Glynn DJ, Thompson JG. Peri‐Conceptual Cytokines – Setting the Trajectory for Embryo Implantation, Pregnancy and Beyond. Am J Reprod Immunol 2011; 66 (Suppl. 1): 2–10Problem The peri‐conceptual environment influences the early embryo to impart long‐term consequences for the fetus and neonate; however, the underlying mechanisms are not well defined.Method of Study We argue that the cytokine network acting in the female reproductive tract during the pre‐ and peri‐implantation period integrates environmental information to program the embryo and fine‐tune the maternal immune response and endometrial remodelling to determine implantation success.Results As well as sex steroid hormones and male seminal fluid factors, female tract cytokines are influenced by agents signalling via the Toll‐like receptors including the microbiome and a plethora of metabolic, chemical and other stressors. In mouse models, an altered peri‐conceptual cytokine environment induced by cytokine deficiency, inflammatory insults or dysregulated seminal fluid signalling is associated with adverse effects on embryo development, pregnancy viability and reproductive outcome.Conclusion The cytokine network provides a pivotal mechanism through which environmental factors influence both embryo development and receptivity of the uterus.

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“…The combination of reducing apoptosis [28], depression immune surveillance [29], as well as the ability to increase the adhesion of the proteolytic activity [30], angiogenic potential proliferation [31], and estrogen production [32] in violation of the innervation determines the ability of this tissue to enhance the implantation and growth on the surface of the peritoneum and, ultimately, the formation, and the occurrence of endometriosis with corresponding symptoms.…”

Section: Changes In the Endometrium Of Endometriosismentioning

confidence: 99%

Innovative approach in assessing the role of neurogenesis, angiogenesis, and lymphangiogenesis in the pathogenesis of external genital endometriosis

Sheveleva¹,

Bejenar

Комличенко

et al. 2016

Gynecological Endocrinology

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Endometriosis is a chronic, progressive, relapsing estrogen-dependent disorder characterized by the growth of tissue structure and function similar to the endometrium outside the normal mucosa of the uterine cavity localization. Endometriosis is found in 10-15% of women in reproductive age and it is one of the main causes of pelvic pain syndrome and infertility. Mechanisms of the development of endometriosis and related pathological pain impulses are still poorly understood and therapeutic approaches do not always have a sufficient effect; in this connection, the study of the pathogenesis of endometriosis and endometriosis-associated pain currently is perspective. Identification of significant factors of angiogenesis, lymphangiogenesis, and neurogenesis in the external genital endometriosis will promote the development of non-invasive early diagnosis and pathogenetic therapy.

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Increased peritoneal and endometrial gene expression of biologically relevant cytokines and growth factors during the menstrual phase in women with endometriosis

Cited by 128 publications

References 25 publications

Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

Peri‐Conceptual Cytokines – Setting the Trajectory for Embryo Implantation, Pregnancy and Beyond

Innovative approach in assessing the role of neurogenesis, angiogenesis, and lymphangiogenesis in the pathogenesis of external genital endometriosis

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