{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:41:36Z","timestamp":1792172496717,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Preeclampsia (PE) differentially impairs female and male fetal endothelial cell function, which is associated with an increased risk of adult\u2010onset cardiovascular disorders in children born to mothers with PE. However, the underlying mechanisms are poorly defined. We hypothesize that dysregulation of microRNA\u201029a\u20103p and 29c\u20103p (miR\u201029a\/c\u20103p) in PE disturbs gene expression and cellular responses to cytokines in fetal endothelial cells in a fetal sex\u2010dependent manner. RT\u2010qPCR analysis of miR\u201029a\/c\u20103p was performed on female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive (NT) pregnancies and PE. Bioinformatic analysis of an RNA\u2010seq dataset was performed to identify PE\u2010dysregulated miR\u201029a\/c\u20103p target genes in female and male P0\u2010HUVECs. Gain\u2010 and loss\u2010of\u2010function assays were conducted to determine the effects of miR\u201029a\/c\u20103p on endothelial monolayer integrity and proliferation in response to transforming growth factor\u2010\u03b21 (TGF\u03b21) and tumour necrosis factor\u2010\u03b1 (TNF\u03b1) in NT and PE HUVECs at passage 1. We observed that PE downregulated miR\u201029a\/c\u20103p in male and female P0\u2010HUVECs. PE dysregulated significantly more miR\u201029a\/c\u20103p target genes in female\n                      <jats:italic>vs<\/jats:italic>\n                      . male P0\u2010HUVECs. Many of these PE\u2010differentially dysregulated miR\u201029a\/c\u20103p target genes are associated with critical cardiovascular diseases and endothelial function. We further demonstrated that miR\u201029a\/c\u20103p knockdown specifically recovered the PE\u2010abolished TGF\u03b21\u2010induced strengthening of endothelial monolayer integrity in female HUVECs, while miR\u201029a\/c\u20103p overexpression specifically enhanced the TNF\u03b1\u2010promoted cell proliferation in male PE HUVECs. In conclusion, PE downregulates miR\u201029a\/c\u20103p expression and differentially dysregulates miR\u201029a\/c\u20103p target genes associated with cardiovascular diseases and endothelial function in female and male fetal endothelial cells, possibly contributing to the fetal sex\u2010specific endothelial dysfunction observed in PE.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15637-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Preeclampsia differentially impairs female and male fetal endothelial cell function in responses to cytokines. Pro\u2010inflammatory cytokines are elevated in maternal circulation during pregnancy in preeclampsia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MicroRNAs are critical regulators of endothelial cell function during pregnancy. We have previously reported that preeclampsia downregulated microRNA\u201029a\u20103p and 29c\u20103p (miR\u201029a\/c\u20103p) in primary fetal endothelial cells. However, it is unknown if PE differentially dysregulates the expression of miR\u201029a\/c\u20103p in female and male fetal endothelial cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We show that preeclampsia downregulates miR\u201029a\/c\u20103p in male and female HUVECs and preeclampsia dysregulates cardiovascular disease\u2010 and endothelial function\u2010associated miR\u201029a\/c\u20103p target genes in HUVECs in a fetal sex\u2010specific manner.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MiR\u201029a\/c\u20103p differentially mediate cell responses to cytokines in female and male fetal endothelial cells from preeclampsia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We have revealed fetal sex\u2010specific dysregulation of miR\u201029a\/c\u20103p target genes in fetal endothelial cells from preeclampsia. This differential dysregulation may contribute to fetal sex\u2010specific endothelial dysfunction in offspring born to preeclamptic mothers.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp284746","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T08:51:27Z","timestamp":1688460687000},"page":"3631-3645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["MicroRNA\u201029 differentially mediates preeclampsia\u2010dysregulated cellular responses to cytokines in female and male fetal endothelial cells"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3349-9069","authenticated-orcid":false,"given":"Chi","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences the University of Arizona Tucson AZ USA"},{"name":"Department of Obstetrics and Gynecology the University of Arizona Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-1221","authenticated-orcid":false,"given":"Colman","family":"Freel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Wisconsin\u2010Madison Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Mills","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences the University of Arizona Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Ran","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences the University of Arizona Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2224-2372","authenticated-orcid":false,"given":"Jing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Wisconsin\u2010Madison Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-021-01138-5"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-014-0018-2"},{"issue":"5","key":"e_1_2_5_4_1","first-page":"1122","article-title":"Hypertension in pregnancy. 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