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In Drosophila, ovulation is induced by mating but also occurs spontaneously in virgins, with rates varying widely in natural populations: short oocyte retention is ancestral, while longer retention is favored in colder climates. The molecular regulation of spontaneous ovulation remains unclear. Here, we show that disrupting the relaxin\/insulin-like peptide Dilp8 or its receptor Lgr3 (an ortholog of vertebrate RXFP1\/2) in follicle cells or specific neurons, respectively, delays ovulation, slows average egg transit time in the reproductive tract, and facilitates oogenesis progression beyond approximately two mature oocytes per ovariole, leading to mature follicle accumulation in the ovary. Mating largely rescues these defects, suggesting the pathway is dispensable post-mating. Dilp8-Lgr3 signaling ensures high oocyte quality by promoting elimination of lower-quality aging oocytes and by antagonizing oogenesis progression via an undefined mechanism downstream of Lgr3-positive neurons. Our findings provide a molecular basis for oocyte retention time regulation in Drosophila involving ovarian-nervous system cross-talk, and bring further support for an ancient, conserved role for relaxin-like signaling in regulating ovulation and overall female reproductive physiology.<\/jats:p>","DOI":"10.1242\/dev.204955","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T07:44:14Z","timestamp":1770623054000},"source":"Crossref","is-referenced-by-count":3,"title":["Dilp8 relaxin signaling from ovarian follicle cells to Lgr3-positive neurons promotes spontaneous ovulation and oocyte quality in\n                    <i>Drosophila<\/i>"],"prefix":"10.1242","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1214-2562","authenticated-orcid":false,"given":"Yanel","family":"Volont\u00e9","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Bah\u00eda Blanca, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas 1 , and Departamento de Biolog\u00eda, Bioqu\u00edmica y Farmacia , , Bah\u00eda Blanca B8000FWB ,","place":["Argentina"]},{"name":"Universidad Nacional del Sur 1 , and Departamento de Biolog\u00eda, Bioqu\u00edmica y Farmacia , , Bah\u00eda Blanca B8000FWB ,","place":["Argentina"]},{"name":"iNOVA4Health, Nova Medical School, NMS, Universidade Nova de Lisboa 2 , Lisbon 1150-082 ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0057-7654","authenticated-orcid":false,"given":"Fabiana","family":"Heredia","sequence":"additional","affiliation":[{"name":"iNOVA4Health, Nova Medical School, NMS, Universidade Nova de Lisboa 2 , Lisbon 1150-082 ,","place":["Portugal"]},{"name":"cE3c - Centre for Ecology, Evolution and Environmental Changes & CHANGE 3 , Departamento de Biologia, Faculdade de Ci\u00eancias , , 1749-016 Lisbon ,","place":["Portugal"]},{"name":"Universidade de Lisboa 3 , Departamento de Biologia, Faculdade de Ci\u00eancias , , 1749-016 Lisbon ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5474-1574","authenticated-orcid":false,"given":"Rebeca","family":"Zanini","sequence":"additional","affiliation":[{"name":"iNOVA4Health, Nova Medical School, NMS, Universidade Nova de Lisboa 2 , Lisbon 1150-082 ,","place":["Portugal"]},{"name":"cE3c - Centre for Ecology, Evolution and Environmental Changes & CHANGE 3 , Departamento de Biologia, Faculdade de Ci\u00eancias , , 1749-016 Lisbon ,","place":["Portugal"]},{"name":"Universidade de Lisboa 3 , Departamento de Biologia, Faculdade de Ci\u00eancias , , 1749-016 Lisbon ,","place":["Portugal"]}]},{"given":"Juliane","family":"Menezes","sequence":"additional","affiliation":[{"name":"iNOVA4Health, Nova Medical School, NMS, Universidade Nova de Lisboa 2 , Lisbon 1150-082 ,","place":["Portugal"]},{"name":"cE3c - Centre for Ecology, Evolution and Environmental Changes & CHANGE 3 , Departamento de Biologia, Faculdade de Ci\u00eancias , , 1749-016 Lisbon ,","place":["Portugal"]},{"name":"Universidade de Lisboa 3 , Departamento de Biologia, Faculdade de Ci\u00eancias , , 1749-016 Lisbon ,","place":["Portugal"]}]},{"given":"Mar\u00eda","family":"Sol Perez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Bioqu\u00edmicas de Bah\u00eda Blanca, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas 1 , and Departamento de Biolog\u00eda, Bioqu\u00edmica y Farmacia , , Bah\u00eda Blanca B8000FWB ,","place":["Argentina"]},{"name":"Universidad Nacional del Sur 1 , and Departamento de Biolog\u00eda, Bioqu\u00edmica y Farmacia , , Bah\u00eda Blanca B8000FWB ,","place":["Argentina"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-6838","authenticated-orcid":false,"given":"Mafalda","family":"Gualdino","sequence":"additional","affiliation":[{"name":"iNOVA4Health, Nova Medical School, NMS, Universidade Nova de Lisboa 2 , Lisbon 1150-082 ,","place":["Portugal"]},{"name":"cE3c - 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Centre for Ecology, Evolution and Environmental Changes & CHANGE 3 , Departamento de Biologia, Faculdade de Ci\u00eancias , , 1749-016 Lisbon ,","place":["Portugal"]},{"name":"Universidade de Lisboa 3 , Departamento de Biologia, Faculdade de Ci\u00eancias , , 1749-016 Lisbon ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0944-3866","authenticated-orcid":false,"given":"Andreia P.","family":"Casimiro","sequence":"additional","affiliation":[{"name":"iNOVA4Health, Nova Medical School, NMS, Universidade Nova de Lisboa 2 , Lisbon 1150-082 ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4243-0298","authenticated-orcid":false,"given":"Catarina C. 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