{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T17:51:00Z","timestamp":1783792260818,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The local environment of the fallopian tube represents the optimal conditions for reproductive processes. To maintain tissue homeostasis, signal transduction pathways are thought to play a pivotal role. Enhancing our understanding of functional signal transduction pathway activity is important to be able to clarify the role of aberrant signal transduction pathway activity leading to female subfertility and other tubal diseases. Therefore, in this study we investigate the influence of the hormonal cycle on the activity of key signal transduction pathways in the fimbrial epithelium of morphologically normal fallopian tubes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>We included healthy pre\u2010 (<jats:italic>n<\/jats:italic>\u00a0=\u00a017) and postmenopausal (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) patients who had surgical interventions for benign gynecologic conditions. Histologic sections of the fallopian tubes were reviewed by two pathologists and, for the premenopausal patients, hormone serum levels and sections of the endometrium were examined to determine the hormonal phase (early follicular [<jats:italic>n<\/jats:italic>\u00a0=\u00a04], late follicular [<jats:italic>n<\/jats:italic>\u00a0=\u00a03], early luteal [<jats:italic>n<\/jats:italic>\u00a0=\u00a05], late luteal [<jats:italic>n<\/jats:italic>\u00a0=\u00a05]). After laser capture microdissection, total mRNA was extracted from the fimbrial epithelium and real\u2010time quantitative reverse transcription\u2010PCR was performed to determine functional signal transduction pathway activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide\u20103\u2010kinase (PI3K), Hedgehog (HH), transforming growth factor\u2010beta (TGF\u2010\u03b2) and canonical wingless\u2010type MMTV integration site (Wnt) pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The early luteal phase demonstrated high AR and ER pathway activity in comparison with the late luteal phase (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.016 and <jats:italic>p<\/jats:italic>\u00a0=\u00a00.032, respectively) and low PI3K activity compared with the late follicular phase (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.036), whereas the late luteal phase showed low activity of HH and Wnt compared with the early follicular phase (both <jats:italic>p<\/jats:italic>\u00a0=\u00a00.016). Signal transduction pathway activity in fimbrial epithelium from postmenopausal patients was most similar to the early follicular and\/or late luteal phase with regard to the AR, ER and PI3K pathways. Wnt pathway activity in postmenopausal patients was comparable to the late follicular and early luteal phase. We observed no differences in HH and TGF\u2010\u03b2 pathway activity between pre\u2010 and postmenopausal samples. The cyclic changes in signal transduction pathway activity suggest a stage\u2010specific function which may affect the morphology and physiology of the human fallopian tube.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated cyclic changes in activity of the AR, ER, PI3K, HH and Wnt pathways throughout the hormonal cycle.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.14306","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T04:14:36Z","timestamp":1639973676000},"page":"256-264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cyclic activity of signal transduction pathways in fimbrial epithelium of the human fallopian tube"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5099-7473","authenticated-orcid":false,"given":"Phyllis","family":"van der Ploeg","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Catharina Hospital  Eindhoven The Netherlands"},{"name":"GROW School for Oncology and Developmental Biology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniek","family":"Uittenboogaard","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Catharina Hospital  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlijn M. M.","family":"Bucks","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Catharina Hospital  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein H. F. M.","family":"Lentjes\u2010Beer","sequence":"additional","affiliation":[{"name":"Laboratory for Pathology and Medical Microbiology (Stichting PAMM)  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Bosch","sequence":"additional","affiliation":[{"name":"Laboratory for Pathology and Medical Microbiology (Stichting PAMM)  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minouche M. E.","family":"van Rumste","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Catharina Hospital  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Caroline","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Elisabeth\u2010TweeSteden Hospital  Tilburg The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"van Diest","sequence":"additional","affiliation":[{"name":"Department of Pathology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrina","family":"Lambrechts","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"van de Stolpe","sequence":"additional","affiliation":[{"name":"Molecular Pathway Dx Philips  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruud L. M.","family":"Bekkers","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Catharina Hospital  Eindhoven The Netherlands"},{"name":"GROW School for Oncology and Developmental Biology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurgen M. J.","family":"Piek","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Catharina Hospital  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-12-0279"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-12-60"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2013.12.015"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006098"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa177"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0000000000001321"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-14-0220"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijgo.2010.07.016"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det246"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2515"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2017.09.012"},{"key":"e_1_2_11_13_1","volume-title":"Haines & Taylor Obstetrical and Gynaecological Pathology","author":"Haines M","year":"2003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.05.020"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-38179-x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11030293"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-19-0318"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0925-4"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.598118"},{"key":"e_1_2_11_20_1","unstructured":"2000 Endotext BG Reed BR Carr KR Feingold B Anawalt A Boyce The normal menstrual cycle and the control of ovulation"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-7-40"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des349"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40695-017-0028-4"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(03)00360-1"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.10.013"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2018.02.002"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2003.09.013"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(00)00204-X"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gam001"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177387"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.105.043182"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)48496-7"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5122(83)90020-8"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2774"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2259"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.05.020"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601128R"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.149989"}],"container-title":["Acta Obstetricia et Gynecologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aogs.14306","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aogs.14306","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aogs.14306","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T15:14:56Z","timestamp":1743779696000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/aogs.14306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,19]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1111\/aogs.14306"],"URL":"https:\/\/doi.org\/10.1111\/aogs.14306","archive":["Portico"],"relation":{},"ISSN":["0001-6349","1600-0412"],"issn-type":[{"value":"0001-6349","type":"print"},{"value":"1600-0412","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,19]]},"assertion":[{"value":"2021-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}