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However, the regulatory effects of PGE2 on endometrial function during the diestrus period and its underlying molecular mechanisms remain poorly understood. Herein, PGE2 treatment promoted the accumulation of lipid droplets and induced cytoskeletal reorganization in bEECs. As a well-established inducer of lipid droplet formation, oleic acid (OA) treatment significantly increased the number of lipid droplets in bEECs, altered the distribution of F-actin and disrupted the expression patterns of key adhesion-related proteins. Transcriptomic analysis revealed that the PPAR signaling pathway was the key pathway that responded to PGE2 treatment in bEECs, and its downstream target gene FABP3 was markedly up-regulated. Knockdown of FABP3 led to a reduced number of BTC spheroids and down-regulation of adhesion-related proteins in bEECs while increasing the density of microvilli and up-regulating the expression of epithelial markers. Prostaglandin E receptor 4 (PTGER4) was the primary receptor that responded to PGE2 treatment, and PTGER4 knockdown or pharmacological inhibition with GW-627368 suppressed FABP3 expression in bEECs. Moreover, uterine samples from dairy cows at different stages of the estrous cycle showed that FABP3 expression was significantly elevated in the endometrium tissue during mid-diestrus compared to metestrus, with predominant localization in the luminal and superficial glandular epithelium. Collectively, these findings indicate that FABP3 regulates lipid droplet accumulation and adhesion ability in bEECs via the PGE2\/PTGER4\/PPAR signaling axis, providing new insights into the metabolic regulation of endometrial receptivity in ruminants.<\/jats:p>","DOI":"10.3390\/ani15233417","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:56:34Z","timestamp":1764165394000},"page":"3417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["FABP3 Mediates Lipid Droplet Accumulation and Adhesive Capacity in Bovine Endometrial Epithelial Cells via PGE2\/PTGER4\/PPAR Axis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0980-2310","authenticated-orcid":false,"given":"Beibei","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"},{"name":"College of Animal Science and Technology, Fujian Vocational College of Agriculture, Fuzhou 350303, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutong","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengfei","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kangkang","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaping","family":"Jin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1749","DOI":"10.1073\/pnas.1721191115","article-title":"Uterine influences on conceptus development in fertility-classified animals","volume":"115","author":"Moraes","year":"2018","journal-title":"Proc. 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