{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:09:29Z","timestamp":1778825369694,"version":"3.51.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["5P50HD098580"],"award-info":[{"award-number":["5P50HD098580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["5T32HD007263-39"],"award-info":[{"award-number":["5T32HD007263-39"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>For a brief but critical period post-fertilization, the mammalian embryo is entirely dependent on maternal products inherited from the oocyte. Previous research showed that oocyte-specific loss of Med12, an X-linked gene and Mediator complex subunit, leads to female sterility despite normal folliculogenesis and ovulation. Here, we show that loss of maternal Med12 has minimal effect on the oocyte transcriptome and does not manifest in embryonic lethality until post-implantation. Implants derived from Med12-null oocytes demonstrate abnormal placentation at E9.5, with an overabundance of trophoblast giant cells (TGC). This phenotype associates with early disruption of lineage markers at the blastocyst stage (e.g., Pou5f1 and Gata3), and later by downregulation of trophoblast pluripotency markers (e.g., Cdx2) and activation of drivers of TGC identity (e.g., Stra13) in the E7.5 extraembryonic ectoderm, revealing a previously undescribed role for Med12 in trophoblast pluripotency maintenance. Notably, we find consistently low Med12 expression in embryos derived from Med12-null oocytes, likely due to programmed paternal X chromosome inactivation (XCI). To isolate the consequences of maternal Med12 depletion, we introduced an autosomal Med12 transgene and show that embryonic expression of the transgene rescues development of Med12-null oocytes. We conclude that oocyte-specific deletion of Med12 produces a maternal-zygotic double knock-out in extraembryonic tissues due to paternal XCI, leading to loss of pluripotency in the trophoblast, placental malformation, and embryonic death.<\/jats:p>","DOI":"10.1093\/biolre\/ioag066","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:39:06Z","timestamp":1774355946000},"page":"1610-1620","source":"Crossref","is-referenced-by-count":0,"title":["Maternal\n                    <i>Med12<\/i>\n                    safeguards trophoblast pluripotency and placental development"],"prefix":"10.1093","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0168-2704","authenticated-orcid":false,"given":"Michelle M","family":"Halstead","sequence":"first","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1661-1936","authenticated-orcid":false,"given":"Jyoti","family":"Goad","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amina","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Febbo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rutuja","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8390-0263","authenticated-orcid":false,"given":"Aleksandar","family":"Rajkovic","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco , San Francisco, CA ,","place":["United States"]},{"name":"Institute of Human Genetics, University of California San Francisco , San Francisco, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"2026051501265811200_ref1","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/S0015-0282(16)58144-8","article-title":"Estimates of human fertility and pregnancy 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