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An In Vivo Method to Study Mouse Blood-Testis Barrier Integrity
Published on: December 2, 2018
A novel effect of polychlorinated biphenyls: impairment of the tight junctions in the mouse epididymis
Jiali Cai1, Chonggang Wang, Lixing Huang
1State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
Abstract:
Polychlorinated biphenyls (PCBs) exhibit a broad range of adverse biological effects, including reproductive toxicity. However, the mechanisms by which PCBs disrupt the epididymis remain obscure. We analyzed the gene expression profile in mice epididymis exposed to PCBs (Aroclor 1254) at doses comparable to human exposure using a cDNA microarray. Differentially expressed genes were involved in a variety of function categories and biological pathways, including GTP binding, nucleosome assembly, and ribosome and protein disulfide isomerase. The differentially expressed genes related to GTP binding were highly enriched. The abundance of GTP binding proteins related to tight junctions being reduced and the phosphorylation level of their downstream effectors were impaired after exposure to PCBs. The results of tracer studies demonstrated that the permeability of blood-epididymis barrier was increased by PCB exposure. In addition, PCB exposure also disrupted the expression of the tight junction proteins, zonula occludens-1 and occludin. We demonstrated for the first time that exposure to PCBs at doses relevant for the general population was able to affect the blood-epididymis barrier in mice through altering GTP binding and tight junction proteins. Our results provided a novel insight into the molecular mechanisms linking PCB exposure to sperm maturation.
Insights
Polychlorinated biphenyls (PCBs) disrupt sperm maturation by damaging the blood-epididymis barrier. This study reveals how PCBs alter GTP binding and tight junction proteins, impacting male reproductive health.
Area of Science:
- Environmental Toxicology
- Reproductive Biology
- Molecular Biology
Background:
- Polychlorinated biphenyls (PCBs) are environmental contaminants with known adverse biological effects, including reproductive toxicity.
- The specific mechanisms by which PCBs disrupt epididymis function, crucial for sperm maturation, are not well understood.
Purpose of the Study:
- To investigate the molecular mechanisms underlying PCB-induced disruption of the epididymis.
- To identify key genes and pathways affected by PCB exposure in the mouse epididymis.
Main Methods:
- Gene expression profiling using cDNA microarray in mice epididymis exposed to Aroclor 1254 (a PCB mixture).
- Analysis of differentially expressed genes, focusing on GTP binding proteins and tight junction components.
- Tracer studies to assess blood-epididymis barrier permeability.
Main Results:
- PCB exposure significantly altered gene expression in the epididymis, with enrichment in GTP binding pathways.
- Reduced abundance of GTP binding proteins associated with tight junctions and impaired phosphorylation of downstream effectors were observed.
- PCB exposure increased blood-epididymis barrier permeability and disrupted the expression of tight junction proteins (zonula occludens-1 and occludin).
Conclusions:
- PCB exposure at environmentally relevant doses affects the blood-epididymis barrier integrity in mice.
- Alterations in GTP binding proteins and tight junction proteins are key molecular mechanisms linking PCB exposure to impaired sperm maturation.
- This study provides novel insights into the molecular basis of PCB reproductive toxicity.

