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Previously, we demonstrated that an environmentally relevant mixture of six antiandrogenic phthalates (PMix), derived from a biomonitoring study in pregnant Brazilian women, was able to disrupt the reproductive development in male rats. Experimental groups (control, 0.1, 0.5, and 500\u2009mg PMix\/kg\/day) were established starting from the extrapolated human dose (0.1\u2009mg\/kg\/day), followed by doses 5 times and 5000 times higher. Pregnant rats received daily oral gavage administration of either vehicle (control) or PMix from gestational day 13 to postnatal day 10. Here, we examined male and female offspring regarding changes in gene expression of key reproductive factors in the hypothalamus and pituitary gland at adulthood and conducted a battery of behavioral tests in males, including partner preference, sexual behavior, and male attractiveness tests. PMix induced some changes in mating\u2010related behavior in males, as demonstrated by the absence of preference for females against males and a higher number of penetrations up to ejaculation in the 0.5 dose group. PMix decreased <jats:italic>Esr2<\/jats:italic> expression in the male hypothalamus across all three doses, and in females at mid and high doses in both the hypothalamus and pituitary. In male hypothalamus, we also observed decreased <jats:italic>Kiss1<\/jats:italic> transcripts in these groups and a reduction in AR at the 0.5 dose group. In summary, our results provide further evidence that phthalates in a mixture, even at low doses, may exert cumulative effects on the structures underlying sexual behavior, which seems to be more sensitive than reproductive endpoints for the same experimental design.<\/jats:p>","DOI":"10.1002\/tox.24414","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T12:58:52Z","timestamp":1725886732000},"page":"54-65","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Phthalates Alters Hypothalamic Gene Expression and Sexual Preference in Rats"],"prefix":"10.1002","volume":"40","author":[{"given":"Tatiana Zauer","family":"Curi","sequence":"first","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology Federal University of Paran\u00e1 (UFPR)  Curitiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella Tapias","family":"Passoni","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology Federal University of Paran\u00e1 (UFPR)  Curitiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Emilia Lima","family":"Tolouei","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology Federal University of Paran\u00e1 (UFPR)  Curitiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anderson Tadeu","family":"de Ara\u00fajo Ramos","sequence":"additional","affiliation":[{"name":"Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology Federal University of Paran\u00e1 (UFPR)  Curitiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samara Christina Fran\u00e7a","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology Federal University of Paran\u00e1 (UFPR)  Curitiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5578-4226","authenticated-orcid":false,"given":"Renata Marino","family":"Romano","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacy State University of Centro\u2010Oeste  Guarapuava Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeane Maria","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacy State University of Centro\u2010Oeste  Guarapuava Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo Roberto","family":"Dalsenter","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology Federal University of Paran\u00e1 (UFPR)  Curitiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5199-2810","authenticated-orcid":false,"given":"Anderson Joel","family":"Martino\u2010Andrade","sequence":"additional","affiliation":[{"name":"Reproductive Toxicology Laboratory, Department of Pharmacology Federal University of Paran\u00e1 (UFPR)  Curitiba Brazil"},{"name":"Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology Federal University of Paran\u00e1 (UFPR)  Curitiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/58.2.350"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.200800312"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230390202335"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh169"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfz159"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2022.02.006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1289\/EHP1443"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12816"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1289\/EHP7662"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2009.01019.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2019.04.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2020.110264"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199903000-00025"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.11.060"},{"key":"e_1_2_10_16_1","first-page":"1","volume-title":"Sexual Differentiation of the Brain and Behavior: A Primer. 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