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
Ovarian tissue explants from one individual were exposed to two MEHP concentrations an epidemiologically relevant 20.05 nM and a 1000-fold higher 20.05 µM or a DMSO control. After six days, single-cell RNA sequencing was performed on the cultured tissue samples using the 10x Genomics single-cell pipeline.
The dataset consists of 18 files in fastq format, compressed with GNUzip (gzip), one file in sha256 format and one file in xlsx format. The total size of the dataset is approximately 69 GB.
Files with open access (2)
Files with open access (2)
Citation and access
Citation and access
Access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
Yes
Type of personal data:
Transcriptomic data
Code key exists:
Yes
Sensitive personal data:
Yes
Citation:
Language:
Method and outcome
Method and outcome
Unit of analysis:
Population:
The samples were obtained from a patient undergoing gender-affirming surgery recruited from Karolinska University Hospital, Huddinge, Sweden.
Time method:
Study design:
- Experimental study
Description of study design:
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.
Sampling procedure:
Number of individuals/objects:
1
Data format/data structure:
Samples/material - Collected from scientific collection/biobank
Samples/material - Collected from scientific collection/biobank
Name:
KI biobank, collection "Miljökemikalier och kvinnlig fertilitet"
Type(s) of sample:
Ovary
Data collection - Registry extract and/or access to biobank sample
Data collection - Registry extract and/or access to biobank sample
Mode of collection:
Registry extract and/or access to biobank sample
Data collector:
- Karolinska Institutet
Opens a new window at ror.org.
ROR
Geographic coverage
Geographic coverage
Geographic location:
Administrative information
Administrative information
Responsible department/unit:
Department of Women's and Children's Health [K6]
Contributor(s):
- Cecilia Lindskog – Uppsala University
Ethical Review
Ethical Review
Reviewer:
- Swedish Ethical Review Authority
components.catalogue.resource.content.administrativeInformation.ethicalReview.rorId.srText
ROR
Registration number:
2021-04563
Reviewer:
- Swedish Ethical Review Authority
components.catalogue.resource.content.administrativeInformation.ethicalReview.rorId.srText
ROR
Registration number:
2015/798-31
Funding
Funding
Funding agency:
Award number:
2018-02280_Formas
Award title:
Phthalates in female reproduction –impact of mixture composition on hazard characterization
Funding information:
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.
Funding agency:
Award number:
2020-01621_Formas
Award title:
Single-cell toxicology for detailed analysis of adverse outcome pathways in human ovary
Funding information:
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.
Funding agency:
- European Union
Award number:
101124440
Award title:
SAfeguarding female FERtility -development of human-relevant in vitro tools for reproductive toxicity
Funding information:
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
Topic and keywords
Topic and keywords
Swedish Standard Classification of Research Subjects 2025:
Relations
Relations
Related resource:
Publications
Publications
Citation:
Single-cell study of human ovarian response to phthalate exposure reveals glial cell susceptibility and disruption of adhesion and mitochondrial pathways
