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Copper deficient mouse embryos are characterized by abnormal yolk sac vasculature and decreased nitric oxide
Author(s) -
Yang Soo Jin,
Lanoue Louise,
Keen Carl L,
Rucker Robert B,
UriuAdams Janet Y
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1066-b
Subject(s) - yolk sac , yolk , embryo , peroxynitrite , nitric oxide , superoxide dismutase , chemistry , medicine , nitrotyrosine , oxidative stress , copper , endocrinology , andrology , nitric oxide synthase , biology , superoxide , biochemistry , microbiology and biotechnology , enzyme , food science , organic chemistry
Copper (Cu) deficiency decreases superoxide dismutase (SOD) activity and increases superoxide anions (O 2 ·− ). Potential consequences of increased O 2 ·− is an increase in peroxynitrite formation and a decrease in increased bioavailable nitric oxide (NO). We have shown that Cu deficient mouse embryos are characterized by elevated nitrotyrosine levels. To test whether this oxidative stress condition alters NO metabolism, gestation day 8.5 embryos from dams fed a Cu adequate (8.0 μg Cu/g; Cu+) or Cu deficient (< 0.5 μg Cu/g; Cu−) diet were cultured in either Cu+ or Cu− medium for 48 h. Cu+/Cu+ and Cu−/Cu− embryos developed similarly, however, Cu−/Cu− embryos showed a high incidence of embryo malformations and yolk sac vessel defects. Vessel diameter distribution data indicated that a higher proportion of vessels from Cu−/Cu− yolk sacs had larger diameter compared to vessels from Cu+/Cu+ yolk sacs. Cu−/Cu− embryos and yolk sacs had lower SOD activity and higher O 2 ·− levels. NO levels were measured (Sievers NO Analyzer 280i) in the media after a 2 h incubation of Cu+/Cu+ and Cu−/Cu− embryos and extra‐embryonic tissues in the presence or absence of NO synthase agonists and inhibitors. Results show that NO levels from Cu−/Cu− embryos, yolk sacs, and ectoplacental cones were lower than Cu+/Cu+ controls under basal (untreated) conditions, and under conditions with the addition of the Ca +2 agonist, ionomycin. These data suggest that decreased NO production and/or bioavailability may contribute to Cu deficiency‐induced embryo malformations and impaired yolk sac vessel development. (Supported by NIH HD26777 and AHA 0465074Y).