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Updated: Oct 21, 2025
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Comparative transcriptomic analysis reveals reproductive impairments caused by PCBs and OH-PCBs through the
Nathan Tam1, Keng Po Lai2, Richard Yuen Chong Kong3
1Department of Chemistry, City University of Hong Kong, Hong Kong, China.
Abstract:
Reports have highlighted the presence of PCBs and their metabolites, OH-PCBs, in human serum as well as their endocrine-disrupting effects on reproductive function through direct interactions with the androgen receptor (AR) and estrogen receptor (ER). However, the molecular mechanisms directly linking the actions of PCBs and OH-PCBs on the AR and ER to induce reproductive impairment remain poorly understood. In this study, we characterized the cellular response to PCBs and OH-PCBs acting on AR and ER transactivation at the transcriptome level coupled with bioinformatics analysis to identify the downstream pathways of androgen and estrogen signaling that leads to reproductive dysfunction. We first confirmed the agonistic and antagonistic effects of several PCBs and OH-PCBs on AR- and ER-mediated reporter gene activity using the androgen-responsive LNCaP and estrogen-responsive MCF-7 cell lines, respectively. Anti-estrogenic activity was not detected among the tested compounds; however, we found that in addition to anti-androgenic and estrogenic activity, PCB 28 and PCB 138 exhibited androgenic activity, while most of the tested OH-PCBs showed a synergistic effect on DHT-mediated transactivation of the AR. Bioinformatics analysis of transcriptome profiles from selected PCBs and OH-PCBs revealed various pathways that were dysregulated depending on their agonistic, antagonistic, or synergistic effects. The OH-PCBs with estrogenic activity affected pathways including vitamin metabolism and calcium transport. Other notable dysregulated pathways include cholesterol transport in response to androgenic PCBs, thyroid hormone metabolism in response to anti-androgenic PCBs, and antioxidant pathways in response to androgen-synergistic OH-PCBs. Our results demonstrate that PCBs and OH-PCBs directly alter specific pathways through androgen- or estrogen-mediated signaling, thereby providing additional insights into the mechanisms by which these compounds cause reproductive dysfunction.
Insights
Polychlorinated biphenyls (PCBs) and their metabolites disrupt reproductive function by interacting with hormone receptors. This study reveals how PCBs and OH-PCBs alter specific cellular pathways, offering new insights into reproductive impairment mechanisms.
Area of Science:
- Environmental Toxicology
- Endocrinology
- Molecular Biology
Background:
- Polychlorinated biphenyls (PCBs) and their metabolites (OH-PCBs) are environmental contaminants found in human serum.
- These compounds are known endocrine disruptors with adverse effects on reproductive function via interactions with androgen (AR) and estrogen (ER) receptors.
- The precise molecular mechanisms linking PCB/OH-PCB actions on AR/ER to reproductive impairment are not fully understood.
Purpose of the Study:
- To characterize the cellular response to PCBs and OH-PCBs at the transcriptome level.
- To identify downstream pathways affected by AR and ER signaling dysregulation caused by PCBs and OH-PCBs.
- To elucidate the molecular mechanisms underlying PCB-induced reproductive dysfunction.
Main Methods:
- Reporter gene assays were used to confirm agonistic/antagonistic effects of PCBs and OH-PCBs on AR and ER activity in LNCaP and MCF-7 cells.
- Transcriptome profiling was performed on cells exposed to selected PCBs and OH-PCBs.
- Bioinformatics analysis was employed to identify dysregulated cellular pathways.
Main Results:
- PCB 28 and PCB 138 exhibited androgenic activity, alongside anti-androgenic and estrogenic effects. Most OH-PCBs showed synergistic effects on AR transactivation.
- Transcriptome analysis revealed dysregulated pathways including vitamin metabolism, calcium transport, cholesterol transport, thyroid hormone metabolism, and antioxidant pathways.
- Specific pathways were altered depending on the compound's agonistic, antagonistic, or synergistic effects via AR or ER signaling.
Conclusions:
- PCBs and OH-PCBs directly modulate specific cellular pathways through AR and ER signaling.
- These alterations provide novel insights into the molecular mechanisms by which these environmental contaminants cause reproductive dysfunction.
- Understanding these pathways is crucial for assessing the risks associated with PCB exposure.
