{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:35:50Z","timestamp":1789702550626,"version":"4.0.1"},"reference-count":21,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["raf.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,9]]},"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-22-0135inf1.jpeg\"\/>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:sec>\n                      <jats:title>Background<\/jats:title>\n                      <jats:p>The distribution of the blood vessel network at any point in time in any body tissue may provide valuable information with regard to the tissue condition, whether it is in a growth, declining or recovery phase as well as giving insights as to its angiogenesis functionality. The blood vessel three-dimensional network of the endometrium goes through a process of change over a relatively short period of 4 weeks on average. It is well accepted that angiogenesis within the endometrium is closely related to the success or failure of the implantation of the embryo.<\/jats:p>\n                    <\/jats:sec>\n                    <jats:sec>\n                      <jats:title>Objective and rationale<\/jats:title>\n                      <jats:p>Our study aims to present a method to follow the three-dimensional evolution of the superficial blood vessel distribution in the endometrium throughout the uterine cycle.<\/jats:p>\n                    <\/jats:sec>\n                    <jats:sec>\n                      <jats:title>Method<\/jats:title>\n                      <jats:p>\n                        This method utilizes differences in the observed broadband colors of the blood vessels in order to assess their depth coordinate below the endometrial tissue surface. We implemented the method using microscopic images of fresh,\n                        <jats:italic>ex vivo<\/jats:italic>\n                        , endometrial samples of different cycle days to obtain the statistical evolution track of the superficial blood vessel population in both human and animal (swine) samples.\n                      <\/jats:p>\n                    <\/jats:sec>\n                    <jats:sec>\n                      <jats:title>Outcomes<\/jats:title>\n                      <jats:p>In human samples, we observed a systematic and consistent trend in the blood vessel diameter distribution at different tissue depths. We demonstrate that the magnitude of this trend evolves throughout the course of the female cycle.<\/jats:p>\n                    <\/jats:sec>\n                    <jats:sec>\n                      <jats:title>Wider implications<\/jats:title>\n                      <jats:p>\n                        This method has the potential to further our understanding of the mechanisms of angiogenesis in tissues other than the endometrium. We propose that this method may also contribute to more precise endometrial dating and may assist in more accurate determination of embryo transfer timing within\n                        <jats:italic>in vitro<\/jats:italic>\n                        fertilization treatments.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>The inner lining tissue of the womb (uterus) is called the endometrium, and it undergoes significant changes during the menstrual cycle.<\/jats:p>\n                    <jats:p>The endometrium blood vessel network goes through rapid changes during the cycle.<\/jats:p>\n                    <jats:p>We have developed a new method to measure this through surface imaging of the endometrium.<\/jats:p>\n                    <jats:p>We use samples of endometrial tissues collected at different dates in the cycle to show how useful this method is in evaluating the development of the endometrium.<\/jats:p>\n                    <jats:p>The method may also be used to investigate different processes of generating new blood vessels and may help to support dating the development of the endometrium.<\/jats:p>\n                    <jats:p>\n                      Our work offers a non-invasive or minimally invasive method which reveals the three-dimensional blood vessel network and may be used to help in a variety of diagnoses. For example, this method may be used to see how receptive the uterus is during\n                      <jats:italic>in vitro<\/jats:italic>\n                      fertilization treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/raf-22-0135","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T10:26:47Z","timestamp":1675938407000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-13","source":"Crossref","is-referenced-by-count":4,"title":["Revealing the uterine blood vessel network via virtual pathology"],"prefix":"10.1530","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4727-4047","authenticated-orcid":true,"given":"Tsafrir S","family":"Kolatt","sequence":"first","affiliation":[{"name":"Iyar \u2013 Institute for Advanced Research, Israel"},{"name":"Fertigo Medical Ltd., Zichron Yaakov, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Shufaro","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Petach Tikva, Israel"},{"name":"The Felsenstein Medical Research Center, the Sackler Faculty of Medicine, Tel-Aviv University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomo","family":"Mashiach","sequence":"additional","affiliation":[{"name":"Assuta Medical Center, Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Czernobilsky","sequence":"additional","affiliation":[{"name":"Patho-Lab Diagnostics Ltd, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarit","family":"Aviel-Ronen","sequence":"additional","affiliation":[{"name":"Assuta Medical Center, Tel-Aviv, Israel"},{"name":"Adelson School of Medicine, Ariel University, Ariel, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liat","family":"Apel-Sarid","sequence":"additional","affiliation":[{"name":"Patho-Lab Diagnostics Ltd, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazal","family":"Dahan","sequence":"additional","affiliation":[{"name":"Fertigo Medical Ltd., Zichron Yaakov, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Or","sequence":"additional","affiliation":[{"name":"Kaplan Medical Center, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Fertility and Sterility","first-page":"788","article-title":"Endometrial dating and determination of the window of implantation in healthy fertile women","volume":"73","author":"Acosta","year":"2000","unstructured":"Acosta AAElberger LBorghi MCalamera JCChemes HDoncel GFKliman HLema BLustig LPapier S2000Endometrial dating and determination of the window of implantation in healthy fertile women. Fertility and Sterility73788\u2013798. (https:\/\/doi.org\/10.1016\/S0015-0282(9900605-6)"},{"key":"bib2","series-title":"Journal of Innovative Optical Health Sciences","first-page":"9","article-title":"Optical properties of skin, subcutaneous, and muscle tissues: a review","volume":"4","author":"Bashkatov","year":"2011","unstructured":"Bashkatov ANGenina EATuchinvV2011Optical properties of skin, subcutaneous, and muscle tissues: a review. Journal of Innovative Optical Health Sciences49\u201338. (https:\/\/doi.org\/10.1142\/S1793545811001319)"},{"key":"bib3","series-title":"Fibroids, menstruation, childbirth, and evolution: the fascinating story of uterine blood vessels","author":"Burbank","year":"2009","unstructured":"Burbank F2009Fibroids, menstruation, childbirth, and evolution: the fascinating story of uterine blood vessels. Tucson, Arizona: Wheatmark."},{"key":"bib4","series-title":"Nature Medicine","first-page":"653","article-title":"Angiogenesis in health and disease","volume":"9","author":"Carmeliet","year":"2003","unstructured":"Carmeliet P2003Angiogenesis in health and disease. Nature Medicine9653\u2013660. (https:\/\/doi.org\/10.1038\/nm0603-653)"},{"key":"bib5","series-title":"Cells, Tissues, Organs","first-page":"94","article-title":"How blood vessel networks are made and measured","volume":"195","author":"Chappell","year":"2012","unstructured":"Chappell JCWiley DMBautch VL2012How blood vessel networks are made and measured. Cells, Tissues, Organs19594\u2013107. (https:\/\/doi.org\/10.1159\/000331398)"},{"key":"bib6","series-title":"Acta Histochemica","first-page":"203","article-title":"Vasculogenesis and angiogenesis in the endometrium during menstrual cycle and implantation","volume":"112","author":"Demir","year":"2010","unstructured":"Demir RYaba AHuppertz B2010Vasculogenesis and angiogenesis in the endometrium during menstrual cycle and implantation. Acta Histochemica112203\u2013214. (https:\/\/doi.org\/10.1016\/J.ACTHIS.2009.04.004)"},{"key":"bib7","series-title":"Developmental Dynamics","first-page":"1704","article-title":"Techniques used to assess intussusceptive angiogenesis: A systematic review","volume":"250","author":"Du Cheyne","year":"2021","unstructured":"Du Cheyne CSmeets MDe Spiegelaere W2021Techniques used to assess intussusceptive angiogenesis: A systematic review. Developmental Dynamics2501704\u20131716. 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(https:\/\/doi.org\/10.1210\/EN.2007-0856)"},{"issue":"Suppl.3","key":"bib12","series-title":"Human Reproduction","first-page":"57","article-title":"The structure of endometrial microvessels","volume":"15","author":"Hickey","year":"2000","unstructured":"Hickey MFraser IS2000The structure of endometrial microvessels. In Human Reproduction15(Suppl.3) 57\u201366. (https:\/\/doi.org\/10.1093\/humrep\/15.suppl_3.57)"},{"key":"bib13","series-title":"Physics in Medicine and Biology","article-title":"Optical properties of biological tissues: a review","volume":"58","author":"Jacques","year":"2013","unstructured":"Jacques SL2013Optical properties of biological tissues: a review. Physics in Medicine and Biology58 R37\u2013R61. (https:\/\/doi.org\/10.1088\/0031-9155\/58\/11\/R37)"},{"key":"bib14","series-title":"Journal of Cellular and Molecular Medicine","first-page":"1491","article-title":"A systems biology view of blood vessel growth and remodelling","volume":"18","author":"Logsdon","year":"2014","unstructured":"Logsdon EAFinley SDPopel ASMacGabhann F2014A systems biology view of blood vessel growth and remodelling. Journal of Cellular and Molecular Medicine181491\u20131508. (https:\/\/doi.org\/10.1111\/jcmm.12164)"},{"key":"bib15","series-title":"Human Reproduction","first-page":"1557","article-title":"Endometrial angiogenesis throughout the human menstrual cycle","volume":"16","author":"Maas","year":"2001","unstructured":"Maas JWMGroothuis PGDunselman GAJDe Goeij AFPMStruyker Boudier HAJEvers JLH2001Endometrial angiogenesis throughout the human menstrual cycle. Human Reproduction161557\u20131561. (https:\/\/doi.org\/10.1093\/HUMREP\/16.8.1557)"},{"key":"bib16","series-title":"Ultrasonography and Reproduction in Swine","author":"Martinat-Bott\u00e9","year":"2000","unstructured":"Martinat-Bott\u00e9 FRenaud GMadec FCostiou PTerqui M2000Ultrasonography and Reproduction in Swine. Paris: INRA."},{"key":"bib17","series-title":"Fertility and Sterility","first-page":"1333","article-title":"A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women","volume":"81","author":"Murray","year":"2004","unstructured":"Murray MJMeyer WRZaino RJLessey BANovotny DBIreland KZeng DFritz MA2004A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertility and Sterility811333\u20131343. (https:\/\/doi.org\/10.1016\/j.fertnstert.2003.11.030)"},{"key":"bib18","series-title":"Fertility and Sterility","first-page":"3","article-title":"Dating the endometrial biopsy","volume":"1","author":"Noyes","year":"1950","unstructured":"Noyes RWHertig ATRock J1950Dating the endometrial biopsy. Fertility and Sterility13\u201325. (https:\/\/doi.org\/10.1016\/S0015-0282(1630062-0)"},{"key":"bib20","series-title":"Human Reproduction Update","first-page":"57","article-title":"Structure and function of endometrial blood vessels","volume":"2","author":"Rogers","year":"1996","unstructured":"Rogers PAW1996Structure and function of endometrial blood vessels. Human Reproduction Update257\u201362. 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