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

Autor: Indusha Kugathas, Hanna K. L. Johansson, Edith Chan Sock Peng, Maryne Toupin, Bertrand Evrard, Thomas A. Darde, Julie Boberg, Monica K. Draskau, Antoine D. Rolland, Séverine Mazaud-Guittot, Frédéric Chalmel, Terje Svingen
Přispěvatelé: Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), National Food Institute [Lyngby] (Forside), SciLicium, This work was funded by the EU Horizon 2020 project FREIA (van Duursen et al. 2020) [grant number 825100]., Chard-Hutchinson, Xavier
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Kugathas, I, Johansson, H K L, Chan Sock Peng, E, Toupin, M, Evrard, B, Darde, T A, Boberg, J, Draskau, M K, Rolland, A D, Mazaud-Guittot, S, Chalmel, F & Svingen, T 2023, ' Transcriptional profiling of the developing rat ovary following intrauterine exposure to the endocrine disruptors diethylstilbestrol and ketoconazole ', Archives of Toxicology, vol. 97, pp. 849-863 . https://doi.org/10.1007/s00204-023-03442-2
Archives of Toxicology
Archives of Toxicology, 2023, 97 (3), pp.849-863. ⟨10.1007/s00204-023-03442-2⟩
ISSN: 0340-5761
1432-0738
DOI: 10.1007/s00204-023-03442-2
Popis: 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.
Databáze: OpenAIRE
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