{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:58:18Z","timestamp":1768489098649,"version":"3.49.0"},"posted":{"date-parts":[[2020,6,24]]},"group-title":"Cell Biology","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization?<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>ACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase and is essential for human endometrial stromal cell decidualization.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>ACE2 is expressed in numerous human tissues including the lungs, heart, intestine, kidneys and placenta. ACE2 is also the receptor by which SARS-CoV-2 enters human cells.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>Proliferative (n = 9) and secretory (n = 6) phase endometrium biopsies from healthy reproductive-age women and primary human endometrial stromal cells from proliferative phase endometrium were used in the study.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>\n                    ACE2 expression and localization were examined by qRT-PCR, Western blot, and immunofluorescence in both human endometrial samples and mouse uterine tissue. The effect of\n                    <jats:italic>ACE2<\/jats:italic>\n                    knockdown on morphological and molecular changes of human endometrial stromal cell decidualization were assessed. Ovariectomized mice were treated with estrogen or progesterone to determine the effects of these hormones on ACE2 expression.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>\n                    In human tissue, ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and expression increases in stromal cells in the secretory phase. The\n                    <jats:italic>ACE2<\/jats:italic>\n                    mRNA (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. HESCs transfected with\n                    <jats:italic>ACE2<\/jats:italic>\n                    -targeting siRNA were less able to decidualize than controls, as evidenced by a lack of morphology change and lower expression of the decidualization markers\n                    <jats:italic>PRL<\/jats:italic>\n                    and\n                    <jats:italic>IGFBP1<\/jats:italic>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). In mice during pregnancy, ACE2 protein was expressed in uterine epithelial and stromal cells increased through day six of pregnancy. Finally, progesterone induced expression of\n                    <jats:italic>Ace2<\/jats:italic>\n                    mRNA in mouse uteri more than vehicle or estrogen (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>LARGE SCALE DATA<\/jats:title>\n                  <jats:p>N\/A.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>\n                    Experiments assessing the function of ACE2 in human endometrial stromal cell decidualization were\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Whether SARS-CoV-2 can enter human endometrial stromal cells and affect decidualization have not been assessed.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>\n                    Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair\n                    <jats:italic>in vivo<\/jats:italic>\n                    decidualization, embryo implantation, and placentation. If so, women with COVID-19 may be at increased risk of early pregnancy loss.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>STUDY FUNDINGS\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>This study was supported by National Institutes of Health \/ National Institute of Child Health and Human Development grants R01HD065435 and R00HD080742 to RK and Washington University School of Medicine start-up funds to RK. The authors declare that they have no conflicts of interest.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2020.06.23.168252","type":"posted-content","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T07:05:19Z","timestamp":1593068719000},"source":"Crossref","is-referenced-by-count":8,"title":["The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization"],"prefix":"10.64898","author":[{"given":"Sangappa B.","family":"Chadchan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vineet K.","family":"Maurya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pooja","family":"Popli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramakrishna","family":"Kommagani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2024080412355970000_2020.06.23.168252v1.1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1080\/17513758.2020.1773000","article-title":"The role of asymptomatic class, quarantine and isolation in the transmission of COVID-19","volume":"14","year":"2020","journal-title":"J Biol Dyn"},{"issue":"1","key":"2024080412355970000_2020.06.23.168252v1.2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/13510002.2020.1763714","article-title":"Renin angiotensin system blockage by losartan neutralize hypercholesterolemia-induced inflammatory and oxidative injuries","volume":"25","year":"2020","journal-title":"Redox Rep"},{"key":"2024080412355970000_2020.06.23.168252v1.3","doi-asserted-by":"crossref","unstructured":"Baud, D. , et al. 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