Single-cell transcriptomic profiling of PM2.5 ovarian toxicity: pulmonary particulate instillation associates with leukocyte infiltration and impaired granulosa cholesterol biosynthesis.

Authors

Lin Zhang, Yongfei Zheng, Xiaotan Shi, Ning Li, Jiaqi Tian, Shuyin Duan

Published in

Toxicology. Pages 154623. Nov 10, 2026. Epub Nov 10, 2026.

Abstract

Ambient fine particulate matter (PM2.5) exposure impairs female reproductive capacity and accelerates follicular depletion, yet ovarian responses remain poorly illustrated at single-cell resolution. To evaluate early multicellular alterations following exposure, we combined a mouse model of repeated pulmonary PM2.5 instillation with single-cell transcriptomic profiling and in situ histological validation. We found that pulmonary PM2.5 instillation expanded the ovarian immune compartment through B-lineage lymphocyte and neutrophil infiltration, whereas resident macrophages adopted a C1qa-enriched scavenger profile without canonical NLRP3 inflammasome activation. At the intercellular interface, immune-derived TGF-β1 and TNF signals engaged somatic receptors and elevated downstream JAK-STAT pathway activity across recipient ovarian somatic cells. Specifically, in follicular granulosa cells, immune-somatic signaling suppressed the cholesterol-biosynthesis program independently of autonomous inflammatory stress, accompanied by matrix remodeling in stromal fibroblasts. Furthermore, dynamic trajectory modeling and in silico perturbation prioritized STAT1 as a candidate regulator of follicular deviation toward atretic fates. Concordantly, in situ multiplex immunofluorescence, TUNEL, and immunohistochemical assays verified parenchymal leukocyte localization, somatic Phospho-STAT1 nuclear engagement, preserved granulosa HMGCR expression, and follicular granulosa apoptosis in intact ovaries. In summary, our findings indicate that pulmonary PM2.5 instillation disrupts ovarian homeostasis through leukocyte infiltration, granulosa sterol suppression, and STAT1-associated follicular atresia.

PMID:
43009125
Bibliographic data and abstract were imported from PubMed on 11 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.