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Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
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Multi-level evidence reveals KCTD15 and FAM19A2 as key targets in PFOA/PFOS-mediated PCOS pathogenesis.
Yuxiao Jiang1, Liying Ge2, Shanshan Zhang3
1Department of Physiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China; School of Life Sciences, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Ecotoxicology and Environmental Safety
|February 20, 2026
Summary
This study links per- and polyfluoroalkyl substances (PFAS) exposure to polycystic ovary syndrome (PCOS) by identifying KCTD15 and FAM19A2 as key genes. Findings suggest a causal association and inform environmental reproductive toxicology research.
Area of Science:
- Environmental Reproductive Toxicology
- Endocrinology
- Computational Biology
Background:
- Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder linked to environmental factors like per- and polyfluoroalkyl substances (PFAS).
- The molecular mechanisms of PFAS-PCOS interactions and their impact on ovarian function are not well understood.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the association between PFAS exposure and PCOS.
- To identify potential molecular targets and causal links between PFAS and PCOS.
Main Methods:
- Utilized in silico absorption, metabolism, distribution, excretion (ADME) profiling and bioinformatics analyses (GEO, GO, KEGG, WGCNA, LASSO).
- Employed Mendelian Randomization (MR) and molecular dynamics simulations (MDS) to assess causality and protein interactions.
- Conducted in vitro experiments on ovarian granulosa cells (GCs) to evaluate the impact of PFAS exposure.
Main Results:
- Identified KCTD15 and FAM19A2 as hub genes associated with PCOS and PFAS exposure.
- Confirmed causal relationships between KCTD15/FAM19A2 and PCOS using MR analyses.
- Demonstrated that PFAS exposure reduces GC viability and alters KCTD15/FAM19A2 expression in vitro, with stable protein binding observed via MDS.
Conclusions:
- KCTD15 and FAM19A2 are identified as potential key genes mediating the effects of PFAS exposure in PCOS.
- Provides preliminary evidence for a causal link between PFAS exposure and PCOS, highlighting potential targets for environmental reproductive toxicology.
