Activation of the lysophosphatidic acid-Lpar3 axis contributes to platelet-rich plasma-induced decidualization

Despite significant advancements in ARTs, nearly 70% of embryo transfers fail, with implantation failure being the primary cause. 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-Lpar3 axis and provide mechanistic insights into its therapeutic potential for improving implantation success.