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Current therapeutic approaches predominantly rely on the single drug praziquantel, highlighting the urgent need to identify additional effective drug targets. G protein-coupled receptors (GPCRs) play important roles in various biological processes and are considered pivotal in drug development. However, the current understanding of the function of GPCRs in schistosomes remains limited.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We conducted a systematic bioinformatics analysis of <jats:italic>Schistosoma japonicum GPCR<\/jats:italic>s using public genomic resources to elucidate their molecular evolution and expression profiles. Selected <jats:italic>GPCR<\/jats:italic>s were functionally characterized using whole-mount in situ hybridization, double fluorescence in situ hybridization, and RNA interference.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Bioinformatics analysis identified 126 <jats:italic>GPCR<\/jats:italic> genes in <jats:italic>S. japonicum<\/jats:italic> and 8 <jats:italic>GPCR<\/jats:italic>s were selected for further studies. qPCR analyses revealed that EWB00_004787 (<jats:italic>Sj-Smo<\/jats:italic>) and EWB00_003955 (<jats:italic>Sj-imGPCR<\/jats:italic>) were significantly enriched in the vitellarium of female worms, where they were found to colocalize with <jats:italic>Sj-DDR48<\/jats:italic>. Following RNAi inhibition of <jats:italic>Sj-Smo<\/jats:italic> and <jats:italic>Sj-imGPCR<\/jats:italic>, cell proliferation in the vitellarium was significantly reduced by 73% and 54%, respectively, and egg productions were also markedly decreased.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This study identifies <jats:italic>Sj-Smo<\/jats:italic> and <jats:italic>Sj-imGPCR<\/jats:italic> as essential regulators of vitellarium development and egg production in <jats:italic>S. japonicum<\/jats:italic>. Targeting these <jats:italic>GPCR<\/jats:italic>s may represent a potentially promising strategy to disrupt egg-mediated pathology and transmission for schistosomiasis control.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s13071-025-06929-2","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T18:22:05Z","timestamp":1752776525000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genome-wide identification and functional characterization of GPCR family genes reveal their key roles in the vitellarium development and egg production in Schistosoma japonicum"],"prefix":"10.1186","volume":"18","author":[{"given":"Xiaoxu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuantao","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofeng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"6929_CR1","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/s1473-3099(21)00090-6","volume":"22","author":"C Kokaliaris","year":"2022","unstructured":"Kokaliaris C, Garba A, Matuska M, Bronzan RN, Colley DG, Dorkenoo AM, Ekpo UF, Fleming FM, French MD, Kabore A, Mbonigaba JB, Midzi N, Mwinzi PNM, N'Goran EK, Polo MR, Sacko M, Tchuem Tchuent\u00e9 LA, Tukahebwa EM, Uvon PA, Yang G, Wiesner L, Zhang Y, Utzinger J, Vounatsou P.\u00a0Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: a spatiotemporal modelling study. 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