Journal article
Polychlorinated biphenyls target Notch/Dll and VEGF R2 in the mouse placenta and human trophoblast cell lines for their anti-angiogenic effects
Scientific reports, Vol.7(1), pp.39885-39885
01/10/2017
DOI: 10.1038/srep39885
PMCID: PMC5223111
PMID: 28071720
Abstract
The intrauterine environment is particularly vulnerable to environmental exposures. We previously established a mouse model that provided evidence for pregnancy complications and placental anti-angiogenesis in response to Aroclor 1254 (A-1254), a mixture of polychlorinated biphenyls (PCBs). Importantly, these effects were observed in IL-10
, but not wild type, mice, suggesting that IL-10 deficiency predisposes to pregnancy disruptive effects of environmental toxicants. However, the mechanisms by which PCBs cause anti-angiogenic effects are unclear. Here, we evaluated PCB-mediated anti-angiogenic effects by diverse but complementary approaches, including HUVEC-mediated trophoblast invasion in nude mice, in vitro three-dimensional capillary tube formation involving HUVEC and/or HTR8 trophoblasts, and aortic ring endothelial cell outgrowth/sprouting. Taken together, our data suggest that PCBs act as potent anti-angiogenic agents. Importantly, we show that treatment of pregnant IL-10
mice with A-1254 resulted in placental activation of the Notch/Delta-like ligand (Dll) pathway, a master regulator of cell-cell interaction and vascular patterning. Similar results were obtained with HUVEC and HTR8 trophoblasts. Rescue of A-1254-induced disruption of HUVEC-based tube formation by γ-secretase inhibitor L1790 confirmed the critical role of the Notch/Dll pathway. Our data suggest that PCBs impart pregnancy disruptive functions by activating the Notch/Dll pathway and by inducing anti-angiogenic effects at the maternal-fetal interface.
Details
- Title: Subtitle
- Polychlorinated biphenyls target Notch/Dll and VEGF R2 in the mouse placenta and human trophoblast cell lines for their anti-angiogenic effects
- Creators
- Satyan Kalkunte - Department of Pediatrics, Women and Infants Hospital of Rhode Island-Warren Alpert Medical School of Brown University, Providence, Rhode Island, USAZheping Huang - Department of Pediatrics, Women and Infants Hospital of Rhode Island-Warren Alpert Medical School of Brown University, Providence, Rhode Island, USAEliana Lippe - Department of Pediatrics, Women and Infants Hospital of Rhode Island-Warren Alpert Medical School of Brown University, Providence, Rhode Island, USASunil Kumar - Division of Reproductive and Cyto-Toxicology, National Institute of Occupational Health (Indian Council of Medical Research), Ahmedabad, Gujarat, IndiaLarry W Robertson - Department of Occupational &Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USASurendra Sharma - Department of Pediatrics, Women and Infants Hospital of Rhode Island-Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7(1), pp.39885-39885
- DOI
- 10.1038/srep39885
- PMID
- 28071720
- PMCID
- PMC5223111
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- England
- Grant note
- P30 ES005605 / NIEHS NIH HHS P20 RR018728 / NCRR NIH HHS P42 ES013661 / NIEHS NIH HHS P42 ES013660 / NIEHS NIH HHS
- Language
- English
- Date published
- 01/10/2017
- Academic Unit
- Occupational and Environmental Health; Iowa Superfund Research Program
- Record Identifier
- 9984002487302771
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