Related Experiment Video
Updated: May 4, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Analyzing the toxicological effects of PET-MPs on male infertility: Insights from network toxicology, mendelian
Yang Yang1, Linfeng Li2, Ning Zhang3
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 218 Jixi Road, Hefei Anhui230022, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University)，Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, Anhui 230032, China; First School of Clinical Medicine, Anhui Medical University, Hefei 230032, China.
Abstract:
Current research indicates that polyethylene terephthalate microplastics (PET-MPs) may significantly impair male reproductive function. This study aimed to investigate the potential molecular mechanisms underlying this impairment. Potential gene targets of PET-MPs were predicted via the SwissTargetPrediction database. GWAS summary statistics for male infertility were obtained from the GWAS Catalog, and eQTL data were acquired from the eQTLGen database. SMR analysis was subsequently performed to identify genes exhibiting significant causal associations with male infertility. The potential targets of PET-MPs contributing to male infertility were ultimately identified by intersecting the two gene sets. Additionally, bulk RNA-seq and scRNA-seq analyses were employed to elucidate the potential molecular mechanisms underlying PET-MPs-induced male infertility. Our findings suggest that CLK4 may serve as a functional target through which PET-MPs contribute to male infertility, with elevated CLK4 expression representing a significant risk factor. Molecular docking and molecular dynamics simulations demonstrated that PET-MPs can form stable binding conformations with the CLK4 protein. We further identified terminally differentiated CD4+ T cells as a prominent risk factor for male infertility, revealing a significant positive correlation between CLK4 expression levels and Th1 cell infiltration. Additionally, CLK4 exhibited a biphasic expression pattern during spermatocyte-to-sperm differentiation, initially increasing before subsequent downregulation. These observations indicate that PET-MPs may participate in the pathogenesis of male infertility by targeting CLK4 to modulate Th1 cell infiltration and disrupt normal spermatogenic processes. In conclusion, our study demonstrates that CLK4 may serve as a potential target for PET-MP-induced male infertility, and we further elucidate the underlying molecular mechanisms.
Insights
Polyethylene terephthalate microplastics (PET-MPs) may harm male fertility. This study identifies CLK4 as a key target, linking PET-MPs to altered T cell infiltration and disrupted sperm development, impacting male reproductive health.
Area of Science:
- Reproductive Biology
- Environmental Toxicology
- Molecular Mechanisms
Background:
- Polyethylene terephthalate microplastics (PET-MPs) are increasingly recognized as environmental contaminants.
- Emerging evidence suggests PET-MPs may negatively impact male reproductive function.
- The precise molecular pathways mediating this impairment remain largely unelucidated.
Purpose of the Study:
- To investigate the molecular mechanisms by which PET-MPs induce male infertility.
- To identify potential gene targets of PET-MPs involved in male reproductive dysfunction.
- To explore the role of CLK4 in PET-MP-associated male infertility.
Main Methods:
- Bioinformatic analyses including SwissTargetPrediction, GWAS, and eQTLGen databases.
- SMR analysis to identify causal associations between genes and male infertility.
- Bulk and single-cell RNA sequencing (scRNA-seq) to analyze gene expression.
- Molecular docking and dynamics simulations to assess PET-MP-CLK4 interactions.
Main Results:
- CLK4 was identified as a functional target of PET-MPs contributing to male infertility.
- Elevated CLK4 expression was associated with increased Th1 cell infiltration and male infertility risk.
- PET-MPs bind to CLK4, disrupting spermatogenesis and modulating T cell responses.
- CLK4 exhibits a biphasic expression pattern during sperm differentiation.
Conclusions:
- CLK4 is a potential molecular target mediating the adverse effects of PET-MPs on male fertility.
- PET-MPs may cause male infertility by targeting CLK4, affecting T cell infiltration and spermatogenic processes.
- Understanding the CLK4-mediated pathway offers insights into environmental impacts on male reproductive health.
