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Transcriptional profiling of developing rat ovary following intrauterine exposure to known endocrine disruptors

ABSTRACT: Transcriptional profiling of developing rat ovary following intrauterine exposure to known endocrine disruptors

PROVIDER: PRJNA860075 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20308500.fastq.gz	Fastqsanger.gz
	SRR20308600.fastq.gz	Fastqsanger.gz
	SRR20308501.fastq.gz	Fastqsanger.gz
	SRR20308601.fastq.gz	Fastqsanger.gz
	SRR20308502.fastq.gz	Fastqsanger.gz

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Transcriptional profiling of developing rat ovary following intrauterine exposure to known endocrine disruptors

Project description:The main objective of the FREIA project is to identify markers of endocrine disrupting effects in rodents to overcome the lack of sensitive markers of female reproductive toxicity. For that 2 archetypes of endocrine disruption are studied, ketoconazole (KTZ) and diethylstilbestrol (DES) at three different stages (post-natal days 6, 14, and 22) and at three different doses 3, 6 and 12 milligram per kilogram by bodyweight per day for KTZ and 3, 6 and 12 microgram per kilogram for DES.

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Project description: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.

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Project description:The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable endocrine disruption (ED) assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17a-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos.

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