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Prenatal diclofenac exposure delays pubertal development and induces behavioral changes in rats.
Krebs Ribeiro, Daniele Cristine; Passoni, Marcella Tapias; Meldola, Heloísa; Curi, Tatiana Zauer; da Silva, Gabriela Neubert; Tolouei, Sara Emilia Lima; Hey, Giovanna Sari; Grechi, Nicole; Dos Santos, Ariany Carvalho; Souza, Roosevelt Isaias Carvalho; Spercoski, Katherinne Maria; Ramos, Anderson Tadeu de Araujo; Martino-Andrade, Anderson Joel.
Afiliación
  • Krebs Ribeiro DC; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • Passoni MT; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • Meldola H; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • Curi TZ; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • da Silva GN; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • Tolouei SEL; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • Hey GS; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • Grechi N; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • Dos Santos AC; Department of Health Sciences, Histopathology Laboratory, Federal University of Grande Dourados (UFGD), Dourados, MS, Brazil.
  • Souza RIC; Department of Health Sciences, Histopathology Laboratory, Federal University of Grande Dourados (UFGD), Dourados, MS, Brazil.
  • Spercoski KM; Department of Biosciences, Federal University of Paraná (UFPR), Palotina, PR, Brazil.
  • Ramos ATA; Department of Physiology, Animal Endocrine and Reproductive Physiology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
  • Martino-Andrade AJ; Department of Pharmacology, Reproductive Toxicology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil; Department of Physiology, Animal Endocrine and Reproductive Physiology Laboratory, Federal University of Paraná (UFPR), Curitiba, PR, Brazil. Electronic address: anderson.andrad
Reprod Toxicol ; 96: 380-389, 2020 09.
Article en En | MEDLINE | ID: mdl-32777255
Diclofenac is a non-steroidal anti-inflammatory drug widely used by the general population and, although generally contraindicated during pregnancy, it is also used by some pregnant women. This study investigated endocrine, reproductive and behavioral effects of diclofenac in male and female offspring rats exposed in utero from gestational days 10-20. Pregnant rats were treated with diclofenac at doses of 0.2, 1 and 5 mg/kg/day via oral gavage. Anogenital distance (AGD), number of nipples, and developmental landmarks of puberty onset - vaginal opening (VO), first estrus (FE) and preputial separation (PPS) - were evaluated in the offspring. At adulthood, behavioral and reproductive parameters were assessed. Male and female rats were tested in the elevated plus maze test to assess locomotor activity and anxiety-like behaviors, while male rats were also evaluated in the partner preference test. No significant effects were observed on AGD and number of nipples in both males and females. Diclofenac treatment induced an overall delay in developmental landmarks of puberty onset in male and female offspring, which reached statistical significance for PPS at the lowest diclofenac dose. Prenatal exposure to all tested doses abolished the preference of male rats for an estrous female, suggesting an impairment of brain masculinization. No changes were observed on male or female reproductive parameters at adulthood. Overall, our results indicate that prenatal exposure to therapeutically relevant doses of diclofenac may have an impact in the pubertal development of rats and negatively affect male partner preference behavior.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Efectos Tardíos de la Exposición Prenatal / Maduración Sexual / Antiinflamatorios no Esteroideos / Diclofenaco Límite: Animals / Pregnancy Idioma: En Revista: Reprod Toxicol Asunto de la revista: EMBRIOLOGIA / MEDICINA REPRODUTIVA / TOXICOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Efectos Tardíos de la Exposición Prenatal / Maduración Sexual / Antiinflamatorios no Esteroideos / Diclofenaco Límite: Animals / Pregnancy Idioma: En Revista: Reprod Toxicol Asunto de la revista: EMBRIOLOGIA / MEDICINA REPRODUTIVA / TOXICOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos