2026-10-07 カロリンスカ研究所（KI）
＜関連情報＞
- https://news.ki.se/phthalates-affected-several-cell-types-in-the-ovary
- https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00371-3/fulltext
ヒト卵巣におけるフタル酸エステル曝露に対する単一細胞レベルでの反応を研究した結果、グリア細胞の感受性、接着経路およびミトコンドリア経路の障害が明らかになった 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∙ et al.
eBioMedicine Published: October 6, 2026
DOI:https://doi.org/10.1016/j.ebiom.2026.106487
Summary
Background
Phthalates 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.
Methods
Ovarian 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.
Findings
Explants 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.
Interpretation
Ovarian 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.
Funding
Swedish Research Council for Sustainable Development and the European Union.
