{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:08:21Z","timestamp":1792786101653,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Natural Science Foundation of China Grant","award":["82571923"],"award-info":[{"award-number":["82571923"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100017607","name":"Shenzhen Fundamental Research Program","doi-asserted-by":"publisher","award":["JCYJ20220530172817039"],"award-info":[{"award-number":["JCYJ20220530172817039"]}],"id":[{"id":"10.13039\/501100017607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017607","name":"Shenzhen Fundamental Research Program","doi-asserted-by":"publisher","award":["JCYJ20240813152902004"],"award-info":[{"award-number":["JCYJ20240813152902004"]}],"id":[{"id":"10.13039\/501100017607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In brief: Chronic endometritis (CE) impairs endometrial receptivity via unknown mechanisms. This study reveals that suppression of the C\/EBP\u03b4\u2013sphingosine kinase 1 (SphK1)\u2013sphingosine-1-phosphate (S1P) axis in CE leads to decidualization defects accompanied by excessive autophagy, providing a mechanistic link between chronic inflammation, sphingolipid dysregulation, and impaired endometrial receptivity.<\/jats:p>\n                  <jats:p>Abstract: Chronic endometritis (CE) is a persistent inflammatory disorder of the endometrium that is increasingly recognized as an important cause of reproductive failure. However, the molecular mechanisms by which CE impairs endometrial receptivity remain incompletely understood. Here, we found that decidualization markers IGFBP1 and PRL were significantly decreased in CE patients, accompanied by abnormal glandular architecture. Transcriptomic analysis revealed sphingolipid metabolism as a dysregulated pathway, with sphingosine kinase 1 (SphK1) markedly downregulated. Sphingosine-1-phosphate (S1P) levels were reduced in both CE tissues and lipopolysaccharide-treated stromal cells during decidualization. Functional experiments confirmed that SphK1 is essential for this process, and its deficiency impairs decidualization. Mechanistically, transcription factor C\/EBP\u03b4 directly bound and activated the SphK1 promoter. Chronic endometritis endometrium showed reduced C\/EBP\u03b4 and SphK1, alongside increased LC3B, indicating autophagic dysregulation. Furthermore, S1P was demonstrated to act extracellularly through the G protein\u2013coupled receptor S1P receptor 3 (S1PR3) to maintain autophagic homeostasis, thereby regulating endometrial decidualization. In conclusion, suppression of the C\/EBP\u03b4\u2013SphK1 axis impairs decidualization with excessive autophagy, revealing a mechanistic link between chronic inflammation, sphingolipid dysregulation, and reproductive failure.<\/jats:p>","DOI":"10.1093\/reprod\/xaag111","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:52:00Z","timestamp":1788616320000},"source":"Crossref","is-referenced-by-count":0,"title":["C\/EBP\u03b4 regulates SPHK1-dependent excessive autophagy in decidualization defects of chronic endometritis"],"prefix":"10.1093","volume":"172","author":[{"given":"Jiahui","family":"Xiao","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics , Shenzhen,","place":["China"]},{"name":"Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital) Department of Reproductive Medicine, , 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