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Proper embryo implantation requires coordinated communication between the blastocyst and a receptive endometrium, particularly through stromal cell decidualization. A thin or poorly responsive endometrium is associated with reduced implantation and pregnancy rates. However, effective treatments for enhancing endometrial receptivity remain limited. Platelet-rich plasma (PRP), which contains growth factors and bioactive molecules, has recently emerged as a promising agent for improving endometrial thickness and fertility outcomes in patients experiencing repeated implantation failures. However, the underlying molecular mechanisms remain unclear. In the present study, we investigated the effects of PRP on the uterus using a pseudopregnant mouse model that mimics the hormonal and endometrial conditions of early pregnancy. We found that intrauterine PRP injection induced decidual-like responses even in the absence of an embryo. Lipidomic analysis revealed that PRP contains high levels of lysophosphatidic acid (LPA), a signaling lipid that promotes decidualization via the G protein-coupled receptor Lpar3. In agreement with the lipidomic data, the injection of pure LPA also evoked decidual reactions. Notably, PRP-induced decidualization was abolished in Lpar3-deficient mice. These findings indicate that PRP exerts its pro-decidual effects through the LPA\u2013Lpar3 axis and provide mechanistic insights into its therapeutic potential for improving implantation success.<\/jats:p>","DOI":"10.1093\/molehr\/gaag022","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:26:25Z","timestamp":1776770785000},"source":"Crossref","is-referenced-by-count":0,"title":["Activation of the lysophosphatidic acid\u2013Lpar3 axis contributes to platelet-rich plasma-induced decidualization"],"prefix":"10.1093","volume":"32","author":[{"given":"Tetsuaki","family":"Kaku","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo , Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7407-4051","authenticated-orcid":false,"given":"Shizu","family":"Aikawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo , Tokyo,","place":["Japan"]},{"name":"Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba , Ibaraki,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuniyuki","family":"Kano","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo , Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiyo","family":"Okudaira","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo , Tokyo,","place":["Japan"]},{"name":"Laboratory of Hospital Pharmacy, School of Pharmacy, Teikyo University , Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamato","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo , Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chihiro","family":"Ishizawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo , Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junken","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo , 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