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Levels of oestrogen receptor, progesterone receptor and alpha B-crystallin in eutopic endometrium in relation to pregnancy in women with endometriosis
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)
2015 (English)In: Human Fertility, ISSN 1464-7273, E-ISSN 1742-8149, Vol. 18, no 1, 30-37 p.Article in journal (Refereed) Published
Abstract [en]

Endometriosis affects fertility in many women and may partly be due to decreased endometrial receptivity. Several mechanisms have been suggested, notably, progesterone resistance for which a number of candidate biomarkers have been suggested. Here we demonstrate aberrant levels of steroid hormone receptors and the small heat shock protein αB-crystallin in eutopic endometrial epithelium from 38 women with peritoneal endometriosis diagnosed during investigation for secondary infertility. Spontaneous pregnancies within 1 year after medical and surgical treatment for endometriosis were recorded and semi-quantitative immunohistochemistry data compared between women with endometriosis who did or did not become pregnant and healthy controls. Stronger immunostaining for ER-α was detected in luminal and glandular endometrial epithelium from women with endometriosis who did not become pregnant during the post-treatment observation period versus endometriosis patients who became pregnant and controls. Staining levels of PR and PR-B were lower in patients without subsequent pregnancies than in the two other groups. Endometrial levels of αB-crystallin in endometriosis patients similar to those in controls were strongly correlated with the chance of becoming pregnant, whereas higher or lower levels were not.

Place, publisher, year, edition, pages
2015. Vol. 18, no 1, 30-37 p.
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
URN: urn:nbn:se:uu:diva-238875DOI: 10.3109/14647273.2014.922705ISI: 000351604500005PubMedID: 24945100OAI: oai:DiVA.org:uu-238875DiVA: diva2:772431
Available from: 2014-12-16 Created: 2014-12-16 Last updated: 2017-12-05Bibliographically 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, ChristianOlovsson, Matts

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