{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:33:15Z","timestamp":1792794795443,"version":"4.5.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Funda\u00e7\u00e3o Arauc\u00e1ria PPSUS 2015","award":["052\/2017"],"award-info":[{"award-number":["052\/2017"]}],"id":[{"id":"https:\/\/ror.org\/02r7nkw81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil (CAPES)\u2014Finance Code 001.","id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dipyrone is an analgesic and antipyretic drug commonly used in many countries. Although generally not recommended during pregnancy, it is known that many women use dipyrone during the gestational period. In this study, we investigated the endocrine and reproductive effects of dipyrone in female and male offspring rats exposed in utero from gestational days 10\u201321. Pregnant rats were treated with dipyrone at 25, 75, and 225\u2009mg\/kg\/day via oral gavage. Developmental landmarks\u2014anogenital index (AGI), number of nipples, vaginal opening, first estrus, and preputial separation\u2014were evaluated in the offspring. Reproductive parameters, including estrous cycle regularity, daily sperm production, weight and histopathology of reproductive organs, steroid hormone levels, and gene expression of selected markers of reproductive function were assessed at adulthood. At the highest dose, dipyrone induced a significant increase in postimplantation losses\/fetal death and delayed parturition in dams. Offspring exposed in utero to the highest dose also exhibited significant changes in some early life markers of endocrine disruption, in particular increased AGI in females, indicating a proandrogenic effect, and increased rate of retained nipples in males, indicating an antiandrogenic response. No changes were observed in markers of puberty onset or reproductive parameters at adulthood. These results suggest that exposure to therapeutically relevant doses of dipyrone may induce mild endocrine disruptive effects that can be detected in late pregnancy and early life. Such effects may be relevant considering dipyrone use by pregnant women and the possibility of coexposures with other endocrine disruptors.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac016","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T15:06:02Z","timestamp":1644764762000},"page":"80-92","source":"Crossref","is-referenced-by-count":7,"title":["The Analgesic Dipyrone Affects Pregnancy Outcomes and Endocrine-Sensitive Endpoints in Female and Male Offspring Rats"],"prefix":"10.1093","volume":"187","author":[{"given":"Marcella Tapias","family":"Passoni","sequence":"first","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele Cristine","family":"Krebs Ribeiro","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samara Christina","family":"Fran\u00e7a de Almeida","sequence":"additional","affiliation":[{"name":"Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Furtado da Costa","sequence":"additional","affiliation":[{"name":"Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Grechi","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Emilia","family":"Lima Tolouei","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana Zauer","family":"Curi","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica","family":"Degraf Cavallin","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory,\u00a0Department of Medicine, State University of Centro-Oeste, 85040-167 Guarapuava, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Marino","family":"Romano","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory,\u00a0Department of Medicine, State University of Centro-Oeste, 85040-167 Guarapuava, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Aur\u00e9lio","family":"Romano","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory,\u00a0Department of Medicine, State University of Centro-Oeste, 85040-167 Guarapuava, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherinne Maria","family":"Spercoski","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Federal University of Paran\u00e1 (UFPR), 85950-000 Palotina, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariany","family":"Carvalho dos Santos","sequence":"additional","affiliation":[{"name":"Histopathology Laboratory, Department of Health Sciences, Federal University of Grande Dourados (UFGD), 79804-970 Dourados, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roosevelt Isaias","family":"Carvalho Souza","sequence":"additional","affiliation":[{"name":"Histopathology Laboratory, Department of Health Sciences, Federal University of Grande Dourados (UFGD), 79804-970 Dourados, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Roberto","family":"Dalsenter","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5199-2810","authenticated-orcid":false,"given":"Anderson Joel","family":"Martino-Andrade","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paran\u00e1 (UFPR), 81531-980 Curitiba, PR, Brazil"},{"name":"Animal 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