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Toxicol Lett ; 303: 48-54, 2019 Mar 15.
Article in English | MEDLINE | ID: mdl-30599193

ABSTRACT

Our goal was to study the effect of BP3 (benzophenone 3) in the follicular assembly and the potential involvement of Foxl2 pathway using whole ovary cultures. Ovaries were collected from Wistar rats at birth, treated in vitro with vehicle (0.01% DMSO), BP3 (5.8 nM, 276 nM, 576 nM and 876 nM) or ESR2 inhibitor (0.1 nM), and cultured for 7 days. Nest breakdown, follicular assembly and the expression of several regulators of these processes (p27, Foxl2, Sox9, Bmp2, Cyp19 and Fst) were evaluated. In vitro exposure to BP3 (5.8 nM) decreased the population of total oocytes, the number of nests per ovary and early primary follicles population. In addition, BP3 (5.8 nM) induced overexpression of Foxl2 mRNA levels through ESR2 but increased Fst mRNA levels independently from ESR2 or Foxl2. We also observed that the number of p27-positive oocytes was decreased after BP3 (5.8 nM). On the other hand, exposure to BP3-276 increased total oocytes, the number of nests per ovary and decreased primary follicles. In addition, BP3-276 induced no changes of Foxl2 mRNA levels through ESR2 but increased Fst mRNA levels independently from ESR2 or Foxl2. In conclusion, our study clearly shows that exposure to BP3 is to perturb the early events of germ cell development as showed here in whole ovary cultures.


Subject(s)
Benzophenones/toxicity , Ovarian Follicle/drug effects , Animals , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolism , Cell Differentiation/drug effects , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Cytochrome P450 Family 19/genetics , Cytochrome P450 Family 19/metabolism , Female , Forkhead Box Protein L2/genetics , Forkhead Box Protein L2/metabolism , Gene Expression Regulation , Germ Cells/drug effects , Germ Cells/growth & development , Oocytes/drug effects , Oocytes/metabolism , Ovarian Follicle/cytology , Ovarian Follicle/metabolism , Rats , Rats, Wistar , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Tissue Culture Techniques
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