{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:55:53Z","timestamp":1781690153573,"version":"3.54.5"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"publisher","award":["2024NSCQ-MSX2667"],"award-info":[{"award-number":["2024NSCQ-MSX2667"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Youth Fund","award":["82205177"],"award-info":[{"award-number":["82205177"]}]},{"name":"Special Funding for Chinese Postdoctoral Research Projects","award":["2023 T160769"],"award-info":[{"award-number":["2023 T160769"]}]},{"name":"Natural Science Fund of Tianjin Municipal Education Commission","award":["2024KJ163"],"award-info":[{"award-number":["2024KJ163"]}]},{"name":"Special Research Fund for Central Universities, Peking Union Medical College","award":["3332024106"],"award-info":[{"award-number":["3332024106"]}]},{"name":"Japan-China Sasakawa Medical Fellowship Program","award":["4408"],"award-info":[{"award-number":["4408"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Advanced maternal age (\u226535\u00a0years) is increasingly common and associated with a higher risk of threatened abortion, yet its molecular basis remains unclear. To elucidate the underlying mechanisms of advanced maternal age-related threatened abortion (AMA-TA) by integrating metabolomics and transcriptomics. Untargeted serum metabolomics was performed in nine AMA-TA patients and seven age-matched healthy pregnant women. An AMA-TA mouse model was established using mifepristone (4\u00a0mg\/kg) to assess embryo resorption, placental morphology, and serum hormone levels. Serum metabolomics and placental transcriptomic profiling (RNA-seq) were then conducted in AMA-TA mice to characterize metabolic and gene expression alterations. Cross-species and multi-omics integration was performed using HomoloGene and MetaboAnalyst 5.0. Key genes were validated by real-time quantitative polymerase chain reaction. Human serum metabolomics revealed the differential metabolites were mainly enriched in steroid hormone biosynthesis, lipid metabolism, and amino-acid metabolism. The AMA-TA model showed higher embryo resorption, abnormal placental architecture, and reduced progesterone and chorionic gonadotropin. RNA-seq revealed 111 up- and 1337 downregulated genes enriched in 68 pathways. Consistently, serum metabolomics in AMA-TA mice also showed significant metabolic disturbances, prominently involving steroid hormone biosynthesis. Integrated analysis converged on steroid hormone biosynthesis as a shared key dysregulated pathway. Real-time quantitative polymerase chain reaction further confirmed aberrant expression of steroid metabolism\u2013related genes, including upregulation of Akr1d1 and Ugt family genes. Disruption of steroid hormone biosynthesis represents central molecular feature of AMA-TA. Integrated multi-omics analysis offers mechanistic insight and supports the development of biomarkers and therapeutic targets for AMA-TA.<\/jats:p>","DOI":"10.1093\/biolre\/ioag045","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T12:39:54Z","timestamp":1772109594000},"page":"2009-2022","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics analysis reveals steroid hormone biosynthesis as a key pathway in advanced maternal age threatened abortion"],"prefix":"10.1093","volume":"114","author":[{"given":"Xia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital , Chongqing 400021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Chengdu Women\u2019s and Children\u2019s Central Hospital University of Electronic Science and Technology of China , Chengdu 611731 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital , Chongqing 400021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aolei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Medical University General Hospital , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Chongqing General Hospital , Chongqing 401147 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Chongqing University Three Gorges Hospital , Chongqing 401500 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital , Chongqing 400021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital , Chongqing 400021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital , Chongqing 400021 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