GEO series

Identification of phthalate mixture exposure targets in the human and mouse ovary in vitro

GSE223645 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 144 samples Submitted 2025/01/27 Platform GPL18573Platform GPL19057

Summary

Chemical health risk assessment is based on single chemicals, but humans and wildlife are exposed to extensive mixtures of industrial substances and pharmaceuticals. Such exposures are life-long and correlate with multiple morbidities, including infertility. How combinatorial effects of chemicals should be handled in hazard characterization and risk assessment are open questions. Further, test systems are missing for several relevant health outcomes including reproductive health and fertility in women. Here, our aim was to screen multiple ovarian cell models for phthalate induced effects to identify biomarkers of exposure. We used an epidemiological cohort study to define different phthalate mixtures for in vitro testing. The mixtures were then tested in five cell models representing ovarian granulosa or stromal cells, namely COV434, KGN, primary human granulosa cells, primary mouse granulosa cells, and primary human ovarian stromal cells. Exposures at epidemiologically relevant exposure level did not markedly elicit cytotoxicity or affect steroidogenesis in short 24-hour exposure. However, significant effects on gene expression were discovered by RNA-sequencing. Altogether, the exposures changed the average expression of 124 genes (9-479 genes per exposure) in human cell models, without obvious concentration or mixture-dependent effects on gene numbers. The mixtures stimulated distinct changes in different cell models. Despite differences, our analyses suggest commonalities in responses towards phthalates, which forms a starting point for follow-up studies on identification and validation of candidate biomarkers that could be developed to novel assays for regulatory testing or even into clinical tests.

Published in

Tarvainen I, Soto DA, Laws MJ et al. · Reproductive toxicology (Elmsford, N.Y.) 2023 · PMID 37160244 · doi:10.1016/j.reprotox.2023.108393

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Direct links to NCBI, no account and no request form: the whole study as GSE223645_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 144 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA927020 and SRA study SRP418925. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 37160244) ↗

Study design

13 conditions, mostly in triplicate

COV434_DMSO ×3 COV434_WQS ×3 COV434_WQS100 ×3 COV434_EPIDEM ×3 COV434_EPIDEM100 ×3 COV434_EQUI ×3 COV434_EQUI100 ×3 COV434_MHHP ×3 +6 more

Supports a between-group comparison across 39 samples.

13 replicated groups read from the first 40 of 144 sample titles; they account for 39 of them. Check it against the sample list below before relying on it.

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