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Endometrial expression of LIF and its receptor and peritoneal fluid levels of IL-1 alpha and IL-6 in women with endometriosis are associated with the probability of pregnancy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
2015 (English)In: Archives of Gynecology and Obstetrics, ISSN 0932-0067, E-ISSN 1432-0711, Vol. 292, no 2, 429-437 p.Article in journal (Refereed) Published
Abstract [en]

To investigate whether eutopic endometrial expression of leukaemia inhibitory factor (LIF), LIF receptor (LIFR) and glycoprotein 130 (gp130) in subfertile women with endometriosis and in healthy controls is related to the probability of spontaneous pregnancy. In addition, we aimed to study peritoneal fluid (PF) levels of interleukin (IL)-1 alpha and IL-6 in the same subsets of women. Eutopic endometrial biopsy and PF samples were taken from patients with rASRM stage I-II endometriosis and healthy controls undergoing laparoscopy. Endometrial LIF, LIFR and gp130 immunostaining and PF levels of IL-1 alpha and IL-6 were assessed. Endometrial biopsy samples were obtained again after postoperative goserelin acetate treatment and on-going pregnancies were registered during a 6-month follow-up period. Reduced endometrial staining of LIF, LIFR and gp130, unaffected by surgery and goserelin, was seen in endometriosis patients without a recorded pregnancy during the study. Elevated PF levels of IL-6 and, in particular, IL-1 alpha were detected in these patients. Reduced eutopic endometrial LIF, LIFR and gp130 protein expression may be associated with subfertility in women with minimal-mild endometriosis. Combined surgical and goserelin acetate treatment does not seem to restore the expression of these members of the IL-6 cytokine superfamily. Elevated peritoneal fluid levels of IL-1 alpha and IL-6 may further contribute to the difficulties of achieving pregnancy in these patients.

Place, publisher, year, edition, pages
2015. Vol. 292, no 2, 429-437 p.
Keyword [en]
Endometriosis, Endometrium, Interleukin, Leukaemia inhibitory factor, Peritoneal fluid, Infertility
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-256979DOI: 10.1007/s00404-015-3626-0ISI: 000355864000030PubMedID: 25631342OAI: oai:DiVA.org:uu-256979DiVA: diva2:838723
Available from: 2015-07-01 Created: 2015-06-29 Last updated: 2017-12-04Bibliographically approved
In thesis
1. The Human Endometrium: Studies on Angiogenesis and Endometriosis
Open this publication in new window or tab >>The Human Endometrium: Studies on Angiogenesis and Endometriosis
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Angiogenesis is thought to play a pivotal role in the cycling endometrium. Coordinated by oestrogen and progesterone, endometrial blood vessel development is primarily mediated by vascular endothelial growth factor-A (VEGF-A), which promotes endothelial cell (EC) proliferation and protects ECs from induced apoptosis. Studying changes at transcript level in human endometrial endothelial cells (HEECs) in response to mitogenic and inhibitory stimuli is one way towards understanding the regulation of physiological endometrial angiogenesis.

Endometriosis, the presence of endometrial-like tissue outside the uterine cavity, is a common gynaecological disorder in women of reproductive age, often causing pelvic pain and reduced fertility. Chronic inflammation in the peritoneal environment and defective endometrial protein expression are some of the contributors to the complex pathophysiology of endometriosis. The aim of this work was to study the changes in the transcriptome induced by VEGF-A and partial serum deprivation in primary HEECs, and to investigate biochemical factors associated with subfertility and chronic pelvic pain in endometriosis patients.

Exposing primary HEECs to VEGF-A, and serum withdrawal was found to regulate transcripts associated with survival, migration, apoptosis and progression through the cell cycle, when assessed using microarray technology and bioinformatic tools. A subset of 88 transcripts was reciprocally regulated under the two experimental conditions; thus probably important in HEEC biology.

Higher endometrial epithelial staining scores of oestrogen receptor-α and reduced staining of progesterone receptors were seen in subfertile endometriosis patients. Lower levels of the receptivity biomarker leukaemia inhibitory factor (LIF) and its receptor, as well as signs of dysregulated αB-crystallin expression and increased peritoneal fluid concentrations of interleukin (IL)-1α and IL-6 were associated with reduced pregnancy rates.

Endometriosis patients with chronic pelvic pain had higher levels of vasoactive intestinal peptide (VIP) in eutopic endometria and in endometriotic lesions compared with patients without chronic pain. The presence of chronic pelvic pain was also associated with increased concentrations of VIP and IL-6 in peritoneal fluid.

The present results may constitute a basis for further investigation of regulatory pathways in endometrial angiogenesis as well as for studies of endometrial receptivity and pain in women with endometriosis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 86 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1299
Keyword
endometrium, angiogenesis, endothelial cell, endometriosis, receptivity, implantation, oestrogen receptor, progesterone receptor, crystallin, interleukin, vasoactive intestinal peptide, peritoneal fluid
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-312493 (URN)978-91-554-9815-3 (ISBN)
Public defence
2017-03-30, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 8683
Available from: 2017-03-08 Created: 2017-01-10 Last updated: 2017-03-13

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Moberg, ChristianBourlev, VladimirIlyasova, NataliaOlovsson, Matts

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