{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:14:29Z","timestamp":1784052869640,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014096","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000}}],"reference-count":115,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GR1549\/7-4"],"award-info":[{"award-number":["GR1549\/7-4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006806","name":"Hollings Cancer Center, Medical University of South Carolina","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010557","name":"Office of the Vice President for Research, University of South Carolina","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010557","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Schistosomiasis is a neglected tropical disease caused by parasitic flatworms of the genus\n                    <jats:italic>Schistosoma<\/jats:italic>\n                    , impacting hundreds of millions of people and animals globally. Disease pathology primarily originates from host immune responses to parasite eggs, which are produced only when female schistosomes are continuously paired with males. Past research focused on pairing-dependent female sexual maturation, while scarce data exist for the male\u2019s reproductive biology. In this study, we characterized the G protein-coupled receptor Sm\n                    <jats:italic>gpcr9<\/jats:italic>\n                    (Smp_244240), an orphan Class A (Rhodopsin-like) GPCR. Previous bulk RNA-seq analyses of adult worms and their isolated gonads revealed that Sm\n                    <jats:italic>gpcr9<\/jats:italic>\n                    belongs to a subgroup of GPCR genes with abundant testis-preferential and pairing-influenced transcript levels in males but low and extremely low expression in unpaired and paired females, respectively. This male-\/unpaired female-biased expression pattern mirrors that of neuropeptide (\n                    <jats:italic>npp<\/jats:italic>\n                    ) genes of\n                    <jats:italic>S. mansoni<\/jats:italic>\n                    such as Sm\n                    <jats:italic>npp26<\/jats:italic>\n                    and Sm\n                    <jats:italic>npp41<\/jats:italic>\n                    . In a deorphanization approach using yeast-two-hybrid analyses, GPCR internalization experiments, bioluminescence resonance energy transfer assays, and by modeling and docking analyses, we provide first evidence that both NPPs can interact with SmGPCR9. Furthermore, we optimized a GPCR RNAi approach and achieved efficient transcript knockdown (&gt; 90%) enabling robust functional characterization of Sm\n                    <jats:italic>gpcr9<\/jats:italic>\n                    . Following RNAi, physiological and morphological analyses revealed that SmGPCR9 regulates key aspects of male reproductive biology like testis morphology and sperm development. Remarkably, ovary structure and egg production were also affected in paired females post RNAi, which could be an indirect effect. We observed similar phenotypes plus motility constraints and reduced stem-cell proliferation in both sexes upon RNAi of Sm\n                    <jats:italic>npp26<\/jats:italic>\n                    and Sm\n                    <jats:italic>npp41<\/jats:italic>\n                    . In all cases, RNAi downstream analyses by RT-qPCR of marker genes substantiated the observed phenotypic effects. These results strongly indicate the importance of SmGPCR9, SmNPP26, and SmNPP41 for spermatogenesis and further physiological processes in male and female\n                    <jats:italic>S. mansoni<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014096","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:38:34Z","timestamp":1783445914000},"page":"e1014096","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["G protein-coupled receptor SmGPCR9 interacts with neuropeptides and controls spermatogenesis in Schistosoma mansoni"],"prefix":"10.1371","volume":"22","author":[{"given":"Saranya","family":"Geetha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Haeberlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Hahnel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Sprague","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri K.","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafqat","family":"Shabir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco H.","family":"Falcone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Buenemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3144-2026","authenticated-orcid":true,"given":"Christoph G.","family":"Grevelding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"issue":"5","key":"ppat.1014096.ref001","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1124\/mol.104.009001","article-title":"The repertoire of G-protein-coupled receptors in fully sequenced genomes","volume":"67","author":"R Fredriksson","year":"2005","journal-title":"Mol Pharmacol"},{"issue":"1","key":"ppat.1014096.ref002","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrd3859","article-title":"The GPCR Network: a 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McManus","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"ppat.1014096.ref035","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ijid.2014.07.009","article-title":"The chronic enteropathogenic disease schistosomiasis","volume":"28","author":"DU Olveda","year":"2014","journal-title":"Int J Infect Dis"},{"key":"ppat.1014096.ref036","volume-title":"Schistosomes: Development, reproduction, and host relations","author":"PF Basch","year":"1991"},{"issue":"5","key":"ppat.1014096.ref037","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S1471-4922(01)01893-1","article-title":"Schistosome male-female interaction: induction of germ-cell differentiation","volume":"17","author":"W Kunz","year":"2001","journal-title":"Trends Parasitol"},{"issue":"14","key":"ppat.1014096.ref038","doi-asserted-by":"crossref","DOI":"10.1016\/j.cub.2004.07.006","article-title":"Schistosoma","volume":"14","author":"CG Grevelding","year":"2004","journal-title":"Curr Biol"},{"issue":"1","key":"ppat.1014096.ref039","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/jez.1402320117","article-title":"Reproductive development of female Schistosoma mansoni (Digenea: Schistosomatidae) following bisexual pairing of worms and worm segments","volume":"232","author":"I Popiel","year":"1984","journal-title":"J Exp Zool"},{"key":"ppat.1014096.ref040","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1017\/S0031182000062697","article-title":"Schistosoma mansoni: male stimulation and DNA synthesis by the female","author":"JE Den Hollander","year":"1985","journal-title":"Parasitology"},{"issue":"11","key":"ppat.1014096.ref041","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0169-4758(91)90263-N","article-title":"Schistosome female reproductive development","volume":"7","author":"PT Loverde","year":"1991","journal-title":"Parasitol 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Res"},{"key":"ppat.1014096.ref045","doi-asserted-by":"crossref","first-page":"605","DOI":"10.2307\/3276242","article-title":"Mating Behavior And Development Of Schistosomes In The Mouse","volume":"51","author":"JC Armstrong","year":"1965","journal-title":"J Parasitol"},{"issue":"1","key":"ppat.1014096.ref046","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/0014-4894(69)90052-6","article-title":"Mating of Schistosoma mansoni in vitro","volume":"25","author":"RM Michaels","year":"1969","journal-title":"Exp Parasitol"},{"issue":"3","key":"ppat.1014096.ref047","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1017\/S003118200005188X","article-title":"A comparative analysis of various developmental stages of Schistosoma mansoni with respect to their protein composition","volume":"75","author":"A Ruppel","year":"1977","journal-title":"Parasitology"},{"issue":"1","key":"ppat.1014096.ref048","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/0014-4894(77)90056-X","article-title":"Schistosoma mansoni: in vitro stimulation of vitelline cell development by extracts of male worms","volume":"42","author":"JR Shaw","year":"1977","journal-title":"Exp Parasitol"},{"issue":"5746","key":"ppat.1014096.ref049","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/283478a0","article-title":"Biochemical basis for the continuous copulation of female Schistosoma mansoni","volume":"283","author":"KH Atkinson","year":"1980","journal-title":"Nature"},{"key":"ppat.1014096.ref050","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0166-6851(84)90064-1","article-title":"Putative polypeptide transfer from male to female Schistosoma mansoni","volume":"11","author":"I Popiel","year":"1984","journal-title":"Mol Biochem 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Dettman","year":"1989","journal-title":"Parasitol Res"},{"key":"ppat.1014096.ref107","doi-asserted-by":"crossref","first-page":"35631","DOI":"10.1038\/srep35631","article-title":"Development of a membrane-anchored ligand and receptor yeast two-hybrid system for ligand-receptor interaction identification","volume":"6","author":"J Li","year":"2016","journal-title":"Sci Rep"},{"issue":"9","key":"ppat.1014096.ref108","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"MW Pfaffl","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"ppat.1014096.ref109","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.pep.2015.02.002","article-title":"Codon optimization of genes for efficient protein expression in mammalian cells by selection of only preferred human codons","volume":"109","author":"S Inouye","year":"2015","journal-title":"Protein Expr 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