{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:48:51Z","timestamp":1789048131558,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Fund of Bulgaria","award":["K\u03a0-06 H31\/2"],"award-info":[{"award-number":["K\u03a0-06 H31\/2"]}]},{"name":"National Science Fund of Bulgaria","award":["PRG1076"],"award-info":[{"award-number":["PRG1076"]}]},{"name":"National Science Fund of Bulgaria","award":["101120075"],"award-info":[{"award-number":["101120075"]}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["K\u03a0-06 H31\/2"],"award-info":[{"award-number":["K\u03a0-06 H31\/2"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG1076"],"award-info":[{"award-number":["PRG1076"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["101120075"],"award-info":[{"award-number":["101120075"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Horizon Europe","award":["K\u03a0-06 H31\/2"],"award-info":[{"award-number":["K\u03a0-06 H31\/2"]}]},{"name":"Horizon Europe","award":["PRG1076"],"award-info":[{"award-number":["PRG1076"]}]},{"name":"Horizon Europe","award":["101120075"],"award-info":[{"award-number":["101120075"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The endometrium, the inner mucosal lining of the uterus, undergoes complex molecular and cellular changes across the menstrual cycle in preparation for embryo implantation. Transcriptome-wide analyses have mainly been utilized to study endometrial receptivity, the prerequisite for successful implantation, with most studies, so far, comparing the endometrial transcriptomes between (i) secretory and proliferative endometrium or (ii) mid-secretory and early secretory endometrium. In the current study, we provide a complete transcriptome description of the endometrium across the entire menstrual cycle and, for the first time, comprehensively characterize the proliferative phase of the endometrium. Our temporal transcriptome analysis includes five time points including the mid-proliferative, late proliferative (peri-ovulatory phase), early secretory, mid-secretory, and late secretory phases. Thus, we unveil exhaustively the transitions between the consecutive proliferative and secretory phases, highlighting their unique gene expression profiles and possible distinct biological functions. The transcriptome analysis reveals many differentially expressed genes (DEGs) across the menstrual cycle, most of which are phase-specific. As an example of coordinated gene activity, the expression profile of histone-encoding genes within the HIST cluster on chromosome 6 shows an increase in cluster activity during the late proliferative and a decline during the mid-secretory phase. Moreover, numerous DEGs are shared among all phases. In conclusion, in the current study, we delineate the endometrial proliferative phase-centered view of transcriptome dynamics across the menstrual cycle. Our data analysis highlights significant transcriptomic and functional changes occurring during the late proliferative phase\u2014an essential transition point from the proliferative phase to the secretory phase. Future studies should explore how the biology of the late proliferative phase endometrium impacts the achievement of mid-secretory endometrial receptivity or contributes to molecular aberrations leading to embryo implantation failure.<\/jats:p>","DOI":"10.3390\/ijms25105320","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:03:08Z","timestamp":1715673788000},"page":"5320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Endometrial Proliferative Phase-Centered View of Transcriptome Dynamics across the Menstrual Cycle"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2507-5735","authenticated-orcid":false,"given":"Apostol","family":"Apostolov","sequence":"first","affiliation":[{"name":"Competence Centre on Health Technologies, 50411 Tartu, Estonia"},{"name":"Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, 17177 Stockholm, Sweden"},{"name":"Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, 17165 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mladen","family":"Naydenov","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Physiology, Faculty of Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aive","family":"Kalinina","sequence":"additional","affiliation":[{"name":"South Estonia Hospital, 65526 V\u00f5ru, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1034-2189","authenticated-orcid":false,"given":"Maria","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Center for Women\u2019s Health, 4000 Plovdiv, Bulgaria"},{"name":"Department of Molecular Biology, Faculty of Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merli","family":"Saare","sequence":"additional","affiliation":[{"name":"Competence Centre on Health Technologies, 50411 Tartu, Estonia"},{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-2465","authenticated-orcid":false,"given":"Elina","family":"Aleksejeva","sequence":"additional","affiliation":[{"name":"Competence Centre on Health Technologies, 50411 Tartu, Estonia"},{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2937-531X","authenticated-orcid":false,"given":"Nadezhda","family":"Milova","sequence":"additional","affiliation":[{"name":"Center for Women\u2019s Health, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0328-9038","authenticated-orcid":false,"given":"Antoan","family":"Milov","sequence":"additional","affiliation":[{"name":"Center for Women\u2019s Health, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-8160","authenticated-orcid":false,"given":"Andres","family":"Salumets","sequence":"additional","affiliation":[{"name":"Competence Centre on Health Technologies, 50411 Tartu, Estonia"},{"name":"Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, 17177 Stockholm, Sweden"},{"name":"Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, 17165 Stockholm, Sweden"},{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, 50406 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5224-9145","authenticated-orcid":false,"given":"Vesselin","family":"Baev","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Yahubyan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S0002-9378(16)33500-1","article-title":"Dating the endometrial biopsy","volume":"122","author":"Noyes","year":"1975","journal-title":"Am. 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