Data for: Single-cell study of human ovarian response to phthalate exposure reveals glial cell susceptibility and disruption of adhesion and mitochondrial pathways
https://doi.org/10.48723/3vtm-jm80
Ovarievävnadsexplantat från en individ exponerades för två koncentrationer av MEHP en epidemiologiskt relevant koncentration på 20,05 nM och en 1000 gånger högre koncentration på 20,05 µM eller en DMSO-kontroll. Efter sex dagars exponering analyserades de odlade vävnadsproverna med enkelcells-RNA-sekvensering (10x Genomics).
Datasetet består av 18 filer i fastq-format, komprimerade med GNUzip (gzip), en fil i sha256-format och en fil i xlsx-format. Datasetets totala storlek är cirka 69 GB.
Dokumentationsfiler
Dokumentationsfiler
Citering och åtkomst
Citering och åtkomst
Tillgänglighetsnivå:
Skapare/primärforskare:
Forskningshuvudman:
Data innehåller personuppgifter:
Ja
Typ av personuppgifter:
Transkriptomiska data
Kodnyckel existerar:
Ja
Data innehåller känsliga personuppgifter:
Ja
Citering:
Språk:
Metod och utfall
Metod och utfall
Analysenhet:
Population:
Proverna togs från en patient som genomgick könsbekräftande kirurgi och som rekryterades från Karolinska Universitetssjukhuset i Huddinge, Sverige
Tidsdimension:
Studiedesign:
- Experimental study
Beskrivning av studiedesign:
Ovarian cortex tissue was exposed for six days to two MEHP concentrations an epidemiologically relevant 20.05 nM and a 1000-fold higher 20.05 µM, with complete media changes and re-exposure every 48 hours. A vehicle control (0·1% DMSO) was included. On day six, explants from one patient (donor 1, 23 years old) were dissociated into single cells for library preparation. Cultured ovarian tissue was dissociated to single cells using a combination of enzymatic and mechanic dissociation. Following dissociation, cells were counted, and viability was assessed to ensure that a high proportion of viable cells (>90% for all samples) proceeded to downstream processing. Three single-cell RNA-sequencing libraries (DMSO, 1X MEHP, 1000X MEHP) were prepared using Chromium Next GEM Single Cell 3’ Reagent Kits v3·1 (10x genomics) according to the manufacturer’s instructions.
Urvalsmetod:
Antal individer/objekt:
1
Dataformat/datastruktur:
Prover/material - Nya från vetenskaplig samling/biobank
Prover/material - Nya från vetenskaplig samling/biobank
Namn:
KI biobank, collection "Miljökemikalier och kvinnlig fertilitet"
Typ(er) av prov:
Ovary
Datainsamling - Registry extract and/or access to biobank sample
Datainsamling - Registry extract and/or access to biobank sample
Insamlingsmetod:
Registry extract and/or access to biobank sample
Datainsamlare:
- Karolinska Institutet
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ROR
Geografisk täckning
Geografisk täckning
Geografisk plats:
Administrativ information
Administrativ information
Ansvarig institution/enhet:
Institutionen för kvinnors och barns hälsa
Medverkande:
- Cecilia Lindskog – Uppsala University
Etikprövning
Etikprövning
Utförare:
- Swedish Ethical Review Authority
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ROR
Diarienummer:
2021-04563
Utförare:
- Swedish Ethical Review Authority
components.catalogue.resource.content.administrativeInformation.ethicalReview.rorId.srText
ROR
Diarienummer:
2015/798-31
Finansiering
Finansiering
Finansiär:
Referensnummer:
2018-02280_Formas
Projektnamn på ansökan:
Phthalates in female reproduction –impact of mixture composition on hazard characterization
Information om finansiering:
Chemical health risk assessment relies on appraisal of single chemicals although it is well known that people are exposed to extensive mixtures. Importantly, experimental studies have demonstrated additive combination effects, emphasizing the need for chemical mixture risk assessment. There is currently a lack of information on how variation in mixture composition impacts risk assessment. Thus, we will utilize different methods for defining mixtures and experimentally study the impact on hazard characterization. Our focus will be on phthalates and female reproduction, a poorly studied system in the field of risk assessment. Our cohort study will define different proportions of phthalates in three mixtures, and the potencies of individual metabolites will be assessed via in vitro experiments to evaluate the dose addition model. Furthermore, cell lines and primary cells of the female reproductive tract will be used to identify novel biomarkers and mechanisms underlying phthalate toxicity via transcriptomics profiling. Identified markers will be validated using 3D cultures of ovarian and endometrial tissue. This project will ultimately provide a systematic comparison of how three analogous phthalate mixtures affect central reproductive processes in women, identify the importance of mixture composition on hazard characterization, and suggest novel biomarkers of human-relevance for reproductive toxicity in women that could be incorporated into regulatory guideline tests.
Finansiär:
Referensnummer:
2020-01621_Formas
Projektnamn på ansökan:
Single-cell toxicology for detailed analysis of adverse outcome pathways in human ovary
Information om finansiering:
Decreasing sperm counts have attracted substantial attention and stimulated discussions about reproductive toxicity of chemicals in men. Similar endpoints have never been measured in women. While semen is easily available and analyzed, oocytes quietly reside in ovarian follicles without giving clear signals of quality or quantity. Nevertheless, recent reviews suggest that female reproductive health may be threatened by chemicals. Our studies on human ovarian tissue have shown that viability, growth and function of follicles can be affected by chemical exposures. However, identification of the underlying mechanisms, which is crucial for development of predictive assays and regulation of chemicals, has proven challenging due to the sheer complexity of ovarian tissue and follicle growth. Ovaries are highly heterogeneous tissue composed of multiple cell populations whose interactions play a crucial role in follicle growth. In addition, cell proportions naturally vary between women. Therefore, subtle changes in differentiation processes and cell-type specific responses can easily be lost in bulk tissue analysis. We have set up a single-cell analysis pipeline for ovarian tissue and mapped all cell types in he human ovary. Here, we will apply this method to analyze ovarian tissue exposed to chemicals on a single-cell level. The results will reveal mechanisms of toxicity in target cell types and aid in building adverse outcome pathways for better chemical health risk assessment.
Finansiär:
- European Union
Referensnummer:
101124440
Projektnamn på ansökan:
SAfeguarding female FERtility -development of human-relevant in vitro tools for reproductive toxicity
Information om finansiering:
The SAFER project develops new in vitro assays to assess reproductive toxicity in women, addressing the gap in chemical safety testing. It utilizes advanced technologies to identify harmful chemicals affecting ovarian function and aims to create animal-free screening tools
Ämnesområde och nyckelord
Ämnesområde och nyckelord
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Relationer
Related resource:
Publikationer
Publikationer
Citering:
Single-cell study of human ovarian response to phthalate exposure reveals glial cell susceptibility and disruption of adhesion and mitochondrial pathways
