Transcriptional profiling of the developing rat ovary following intrauterine exposure to the endocrine disruptors diethylstilbestrol and ketoconazole.

Autor: Kugathas I; Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, 9 avenue du Professeur Léon Bernard, 35000, Rennes, France., Johansson HKL; National Food Institute, Technical University of Denmark, Kemitorvet, Building 202, 2800, Kongens Lyngby, Denmark., Chan Sock Peng E; Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, 9 avenue du Professeur Léon Bernard, 35000, Rennes, France., Toupin M; Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, 9 avenue du Professeur Léon Bernard, 35000, Rennes, France., Evrard B; Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, 9 avenue du Professeur Léon Bernard, 35000, Rennes, France., Darde TA; SciLicium, 10 rue de la Sauvaie, 35200, Rennes, France., Boberg J; National Food Institute, Technical University of Denmark, Kemitorvet, Building 202, 2800, Kongens Lyngby, Denmark., Draskau MK; National Food Institute, Technical University of Denmark, Kemitorvet, Building 202, 2800, Kongens Lyngby, Denmark., Rolland AD; Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, 9 avenue du Professeur Léon Bernard, 35000, Rennes, France., Mazaud-Guittot S; Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, 9 avenue du Professeur Léon Bernard, 35000, Rennes, France., Chalmel F; Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, 9 avenue du Professeur Léon Bernard, 35000, Rennes, France. frederic.chalmel@inserm.fr., Svingen T; National Food Institute, Technical University of Denmark, Kemitorvet, Building 202, 2800, Kongens Lyngby, Denmark. tesv@food.dtu.dk.
Jazyk: angličtina
Zdroj: Archives of toxicology [Arch Toxicol] 2023 Mar; Vol. 97 (3), pp. 849-863. Date of Electronic Publication: 2023 Jan 18.
DOI: 10.1007/s00204-023-03442-2
Abstrakt: Exposure to endocrine-disrupting chemicals (EDCs) during development may cause reproductive disorders in women. Although female reproductive endpoints are assessed in rodent toxicity studies, a concern is that typical endpoints are not sensitive enough to detect chemicals of concern to human health. If so, measured endpoints must be improved or new biomarkers of effects included. Herein, we have characterized the dynamic transcriptional landscape of developing rat ovaries exposed to two well-known EDCs, diethylstilbestrol (DES) and ketoconazole (KTZ), by 3' RNA sequencing. Rats were orally exposed from day 7 of gestation until birth, and from postnatal day 1 until days 6, 14 or 22. Three exposure doses for each chemical were used: 3, 6 and 12 µg/kg bw/day of DES; 3, 6, 12 mg/kg bw/day of KTZ. The transcriptome changed dynamically during perinatal development in control ovaries, with 1137 differentially expressed genes (DEGs) partitioned into 3 broad expression patterns. A cross-species deconvolution strategy based on a mouse ovary developmental cell atlas was used to map any changes to ovarian cellularity across the perinatal period to allow for characterization of actual changes to gene transcript levels. A total of 184 DEGs were observed across dose groups and developmental stages in DES-exposed ovaries, and 111 DEGs in KTZ-exposed ovaries across dose groups and developmental stages. Based on our analyses, we have identified new candidate biomarkers for female reproductive toxicity induced by EDC, including Kcne2, Calb2 and Insl3.
(© 2023. The Author(s).)
Databáze: MEDLINE
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