Evidence map›Paper›PMID 42838884›Full record

ArticleEBioMedicine2026

Single-cell study of human ovarian response to phthalate exposure reveals glial cell susceptibility and disruption of adhesion and mitochondrial pathways.

Eleftheria Maria Panagiotou, Loren Méar, Ilmatar Rooda, Alesandro Haxhiu, Elisabeth Moussaud-Lamodière, Karolina Wasilewska, Tianyi Li, Catarina Arnelo, Karin Pettersson, Kiriaki Papaikonomou and 2 more

Abstract read
In one paragraph

Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Eleftheria Maria PanagiotouDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
Loren MéarDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Immunology, Genetics and Pathology, Cancer Precision Medicine, Uppsala University, Uppsala, Sweden.
Ilmatar RoodaDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
Alesandro HaxhiuDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
Elisabeth Moussaud-LamodièreDepartment of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Karolina WasilewskaDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
Tianyi LiDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Catarina ArneloDepartment of Pregnancy and Delivery, Karolinska University Hospital, Stockholm, Sweden.
Karin PetterssonDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Kiriaki PapaikonomouDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
Cecilia LindskogDepartment of Immunology, Genetics and Pathology, Cancer Precision Medicine, Uppsala University, Uppsala, Sweden.
Pauliina DamdimopoulouDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden. Electronic address: pauliina.damdimopoulou@ki.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPhthalates are known male endocrine disruptors and reproductive toxicants. Despite growing evidence of female effects, mechanistic knowledge in key reproductive organs remains limited, hindering regulations. Here, we conducted an experimental study to map the impact of mono(2-ethylhexyl) phthalate (MEHP), the primary metabolite of di(2-ethylhexyl) phthalate (DEHP), on adult human ovarian tissue at single-cell resolution.

methodsOvarian tissue explants from seven donors (five gender-affirming surgery, two caesarean-section) were exposed to two MEHP concentrations: an epidemiologically relevant 20.51 nM and a 1000-fold higher 20.51 μM. After six days, single-cell RNA sequencing (one donor) and immunostainings (six donors) were used to characterise gene expression changes across cell types. Primary ovarian cells derived from three gender-affirming surgery patients and stem cell-derived Schwann cells were used for validation.

findingsExplants retained all major ovarian cell types, including rare glial cells and oocytes. MEHP altered transcriptomes across all cell types, disrupting pathways related to actin cytoskeleton, cell adhesion, and oxidative phosphorylation (OXPHOS). Protein analyses confirmed altered EIF5A, MT-ND3, MT-ND4L, and VCL expression, genes linked to mitochondrial translation, OXPHOS, adhesion, and cytoskeleton. MEHP also reduced cell-cell communication, particularly glial-stromal interactions. Mitochondrial stress assay in primary cells indicated increased proton leakage, and Schwann cell responses mirrored the scRNA-seq findings.

interpretationOvarian toxicity studies traditionally focus on follicles, but this study reveals the susceptibility of non-follicular cells. Importantly, the sensitivity of ovarian nervous system cells to MEHP offers new mechanistic insights into reported links between phthalates, altered ovarian sensitivity index, and polyendocrine metabolic ovarian syndrome. Our findings highlight the need for a holistic assessment of ovarian toxicity that considers all ovarian cell types, not only follicles.

fundingSwedish Research Council for Sustainable Development and the European Union.

Indexed as

Diethylhexyl PhthalateMitochondriaNeurogliaOvaryPhthalic AcidsSingle-Cell AnalysisAdultCell AdhesionFemaleGene Expression ProfilingGene Expression RegulationHumansSingle-Cell Gene Expression AnalysisTranscriptomeDiethylhexyl Phthalatemono-(2-ethylhexyl)phthalatePhthalic AcidsEndocrine disrupting chemicalsFemale fertilityHuman ovaryPhthalatesSingle cell RNA sequencingTissue explant culture

Identifiers

PMID42838884
PMCPMC13688040

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.