{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:25:42Z","timestamp":1787221542777,"version":"build-2736575974"},"reference-count":36,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["raf.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                    <jats:p>\n                      <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"images\/RAF-21-0093inf1.jpeg\"\/>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Recurrent reproductive failure (RRF) encompasses recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). These highly prevalent, distressing conditions have many unanswered questions regarding aetiology and management. Oestrogen receptor beta (ER\u03b2) is the predominant oestrogen receptor expressed in the vascular endothelium of the endometrium during the window of implantation (WOI). The establishment of normal endometrial receptivity is integrally associated with progesterone receptor (PR). Therefore, we aimed to investigate whether women with RRF have clinical, type-specific endometrial aberrations of ER\u03b2, PR and Ki-67 expression during the WOI. Thirty-eight endometrial biopsies were collected; 29 RRF (10 RIF, 9 recurrent loss of early pregnancy (RLEP) and 10 recurrent fetal loss (RFL)) and 9 fertile controls (FC). Within RIF, RLEP and RFL groups, the perivascular compartment showed significantly lower levels of ER\u03b2 vs FC (\n                      <jats:italic>P\u2009\u2009=\u2009<\/jats:italic>\n                      0.02\n                      <jats:italic>, P\u2009\u2009=\u2009<\/jats:italic>\n                      0.03 and\n                      <jats:italic>P\u2009\u2009=\u2009<\/jats:italic>\n                      0.01, respectively). Vascular endothelium also displayed significantly lower levels of ER\u03b2 within RIF and RFL cohorts vs FC (\n                      <jats:italic>P\u2009\u2009=\u2009<\/jats:italic>\n                      0.03 and\n                      <jats:italic>P\u2009\u2009=\u2009<\/jats:italic>\n                      0.003). The expression of Ki-67 was significantly lower within vascular endothelium of all RRF; RIF (\n                      <jats:italic>P\u2009\u2009=\u2009<\/jats:italic>\n                      0.02), RLEP (\n                      <jats:italic>P\u2009\u2009=\u2009<\/jats:italic>\n                      0.02) and RFL (\n                      <jats:italic>P\u2009 &lt;<\/jats:italic>\n                      0.01). PR was significantly reduced (\n                      <jats:italic>P\u2009 &lt;<\/jats:italic>\n                      0.001) in the perivascular area of women with RIF. These findings provide novel insights into biological correlates of clinical subtypes of RRF. The endometrium of women with RRF display significantly altered levels of ER\u03b2, PR and Ki-67 during the WOI, furthering our understanding of the defective endometrial phenotype of women suffering from RRF, with possible impaired glandular function, angiogenesis and decidualisation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>Recurrent reproductive failure (RRF) refers to a group of devastating conditions with many unanswered questions regarding their causes and treatment options. The lining of the womb, the endometrium, is primed and suitable for successful embryo implantation for a short time during the menstrual cycle; the window of implantation (WOI). Oestrogen is a key hormone that plays an important role in regulating the endometrium and its effects are exerted via two oestrogen receptor subtypes. Oestrogen receptor beta (ER\u03b2) is the main oestrogen receptor present during the WOI. Progesterone receptor allows the other main hormone, progesterone, to influence the endometrial activity and Ki-67 reflects the proliferative activity of the cells within the endometrium. We investigated the expression of these markers in endometrial samples collected from women with RRF and proven fertility. We found that the endometrium of women with RRF has significantly lower levels of ER\u03b2 and Ki-67 during the WOI, possibly leading to unsuccessful pregnancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/raf-21-0093","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T12:32:29Z","timestamp":1645533149000},"page":"30-38","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-13","source":"Crossref","is-referenced-by-count":18,"title":["Altered endometrial oestrogen-responsiveness and recurrent reproductive failure"],"prefix":"10.1530","volume":"3","author":[{"given":"Hannan","family":"Al-Lamee","sequence":"first","affiliation":[{"name":"Centre for Women\u2019s Health Research, Department of Women\u2019s and Children\u2019s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool, UK"},{"name":"Liverpool Women\u2019s NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool, UK"},{"name":"Hewitt Centre for Reproductive Medicine, Liverpool Women\u2019s NHS Foundation Trust, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Ellison","sequence":"additional","affiliation":[{"name":"Centre for Women\u2019s Health Research, Department of Women\u2019s and Children\u2019s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Drury","sequence":"additional","affiliation":[{"name":"Centre for Women\u2019s Health Research, Department of Women\u2019s and Children\u2019s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Hill","sequence":"additional","affiliation":[{"name":"Centre for Women\u2019s Health Research, Department of Women\u2019s and Children\u2019s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Drakeley","sequence":"additional","affiliation":[{"name":"Liverpool Women\u2019s NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool, UK"},{"name":"Hewitt Centre for Reproductive Medicine, Liverpool Women\u2019s NHS Foundation Trust, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0270-0150","authenticated-orcid":true,"given":"Dharani K","family":"Hapangama","sequence":"additional","affiliation":[{"name":"Centre for Women\u2019s Health Research, Department of Women\u2019s and Children\u2019s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool, UK"},{"name":"Liverpool Women\u2019s NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3633-1592","authenticated-orcid":true,"given":"Nicola","family":"Tempest","sequence":"additional","affiliation":[{"name":"Centre for Women\u2019s Health Research, Department of Women\u2019s and Children\u2019s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool, UK"},{"name":"Liverpool Women\u2019s NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool, UK"},{"name":"Hewitt Centre for Reproductive Medicine, Liverpool Women\u2019s NHS Foundation Trust, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Cancers","article-title":"Aberrant dyskerin expression is related to proliferation and poor survival in endometrial cancer","volume":"13","author":"Alnafakh","year":"2021","unstructured":"Alnafakh RSaretzki GMidgley AFlynn JKamal AMDobson LNatarajan PStringfellow HMartin-Hirsch PDeCruze SB2021Aberrant dyskerin expression is related to proliferation and poor survival in endometrial cancer. 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