Molecular mechanisms of environmental toxin cadmium at the feto-maternal interface investigated using an organ-on-chip (FMi-OOC) model

JOURNAL OF HAZARDOUS MATERIALS

卷:422

Article

Kim, Sungjin¹  Richardson, Lauren^1,2  Radnaa, Enkhtuya²  Chen, Zunwei³  Rusyn, Ivan³  Menon, Ramkumar²  Han, Arum¹ 

[1] Texas A&M Univ, Dept Elect & Comp Engn, College Stn, TX USA

[2] Univ Texas Med Branch, Div Maternal Fetal Med & Perinatal Res, Dept Obstet & Gynecol, 301 Univ Blvd, Galveston, TX 77555 USA

[3] Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX USA

关键词: Organ-on-chip;    Fetal membrane;    Inflammation;    Decidua;    Preterm birth;    Toxicity testing;    Cadmium toxicity;   

DOI  :  10.1016/j.jhazmat.2021.126759

来源: Elsevier

【 摘 要 】

Human labor is associated with feto-maternal-derived signals that coordinate to initiate delivery. Exposure to environmental chemicals can prematurely trigger labor-initiating signals at the feto-maternal interface (FMi: decidua, amniochorion), leading to spontaneous preterm birth (PTB). Testing the association between environmental chemical exposure and PTB is difficult due to many limitations in vivo or in vitro. Physiological organon-chips (OOCs) are potential alternatives for studying mechanisms leading to PTB. The presented study tested the effect of maternal exposure to cadmium (Cd), an environmental toxin, using the FMi-OOC that incorporates maternal decidua cells and three different fetal cells (chorion, amnion mesenchymal, and amnion epithelial cells). Cd transport through the FMi and its impact on cell cycle, cell death, and inflammation were analyzed. Cd treatment resulted in significant cell death and a pro-inflammatory environment in the maternal decidua, but had minimal effect on the fetal chorion cells, and no effect in the fetal amnion cells compared to controls. The maternal response, but lack of fetal response, indicates that Cd-mediated adverse effects originate from maternal pathophysiology rather than fetal-derived triggers of preterm labor. This study demonstrates that the FMi-OOC can indeed predict the response of FMi upon exposure to chemicals, opening the possibility for using OOC models for environmental toxin screens.

【 授权许可】

Free