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Placenta from PE patients releases harmful factors that contribute to the exacerbation of the disease. Among these factors is the prokineticin1 (PROK1) and its receptor, PROKR2 that we identified as a mediators of PE. Here we tested the effects of PKRA, an antagonist of PROKR2, on the attenuation of PE symptoms. We used the genetic PE mouse model, STOX1 that overexpresses <jats:italic>Stox1<\/jats:italic> gene in a heterozygosis manner in the placenta. This model allowed exploiting two genotypes of the offspring, those that overexpress the <jats:italic>Stox1<\/jats:italic> gene, and the WT that grow in a PE environment (STE). We characterised the effect PKRA (1\u2009\u03bcM) on the attenuation of PE symptoms and compared its effects on STOX1 and STE placentas. We also used <jats:italic>STOX1<\/jats:italic> overexpressing trophoblast cells to decipher the PROK1\u2010underlying mechanism. We demonstrated that (i) antagonisation of PROKR2 attenuated PE\u2010mediated hypertension and proteinuria, (ii) STE placentas and foetuses exhibited better outcomes in response to PKRA, (iii) the secretome of STOX1\u2010trophoblasts impacted the integrity of the fetal vasculature that was attenuated by PKRA treatment. This study demonstrates the direct involvement of the PROK1 in PE and identifies PKRA as a promising therapy for PE.<\/jats:p>","DOI":"10.1111\/jcmm.70346","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T13:40:21Z","timestamp":1737034821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antagonisation of Prokineticin Receptor\u20102 Attenuates Preeclampsia Symptoms"],"prefix":"10.1111","volume":"29","author":[{"given":"Fr\u00e9d\u00e9ric","family":"Sergent","sequence":"first","affiliation":[{"name":"Interdisciplinary Research Institute of Grenoble, IRIG\u2010Biosant\u00e9 University Grenoble Alpes, INSERM, CEA, UMR 1292  Grenoble France"},{"name":"Commissariat \u00e0 l'Energie Atomique et Aux Energies Alternatives (CEA) Biosciences and Biotechnology Institute of Grenoble  Grenoble 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