{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:15:38Z","timestamp":1791591338383,"version":"4.3.4"},"posted":{"date-parts":[[2024,3,21]]},"group-title":"Molecular Biology","reference-count":50,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  African-American women have a maternal mortality rate approximately three times higher than European-American women. This is partially due to hypertensive disorders of pregnancy, including preeclampsia. Fetal\n                  <jats:italic>APOL1<\/jats:italic>\n                  high-risk genotype increases preeclampsia risk, although mechanisms remain elusive. We characterized two mouse models to investigate whether fetal-origin APOL1 induces preeclampsia and which cell types contribute. We\n                  <jats:italic>in vitro<\/jats:italic>\n                  fertilized mice with sperm from two transgenic mouse lines:\n                  <jats:italic>APOL1<\/jats:italic>\n                  transgenic mice carrying human genomic locus constructs from bacterial artificial chromosomes (BAC) containing the\n                  <jats:italic>APOL1<\/jats:italic>\n                  gene, mimicking expression and function of human APOL1 (BAC\/APOL1 mice) and albumin promoter\n                  <jats:italic>APOL1<\/jats:italic>\n                  transgenic mice expressing\n                  <jats:italic>APOL1<\/jats:italic>\n                  in liver and plasma (Alb\/APOL1 mice). Dams carrying either BAC\/APOL1-G1 or Alb\/APOL1-G1 fetuses had elevated systolic blood pressure, while dams carrying BAC\/APOL1-G0 or Alb\/APOL1-G0 fetuses did not. BAC\/APOL1-G1 and Alb\/APOL1-G1 fetuses weighed less than littermates, indicating intrauterine growth restriction. Single-nucleus RNA-seq of APOL1-G1 placentas showed increased expression of osteopontin\/Spp1, most prominently in vascular endothelial cells with robust APOL1 expression. Cell-cell interaction analysis indicated pro-inflammatory signaling between placental cells and maternal monocytes. These models show that fetal origin APOL1-G1 causes preeclampsia, inducing pro-inflammatory response in placenta and maternal monocytes. The APOL1-G1 variant poses a multi-generational problem, causing effects in mothers and offspring.\n                <\/jats:p>","DOI":"10.1101\/2024.03.20.586039","type":"posted-content","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T23:30:26Z","timestamp":1711063826000},"source":"Crossref","is-referenced-by-count":5,"title":["Preeclampsia in mice carrying fetuses with APOL1 risk variants"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2049-7347","authenticated-orcid":false,"given":"Teruhiko","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khun Zaw","family":"Latt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi","family":"Shrivastav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly J.","family":"Reidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Charlton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl A.","family":"Winkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E.","family":"Reznik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi Z.","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Kopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024033121000497000_2024.03.20.586039v2.1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000003891"},{"key":"2024033121000497000_2024.03.20.586039v2.2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.681632"},{"key":"2024033121000497000_2024.03.20.586039v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.08.014"},{"key":"2024033121000497000_2024.03.20.586039v2.4","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000208"},{"key":"2024033121000497000_2024.03.20.586039v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0119-6"},{"key":"2024033121000497000_2024.03.20.586039v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.07.038"},{"key":"2024033121000497000_2024.03.20.586039v2.7","doi-asserted-by":"publisher","DOI":"10.15620\/cdc:124678"},{"key":"2024033121000497000_2024.03.20.586039v2.8","unstructured":"KFF. 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