In vivo and in vitro developmental toxicity in LPS-induced zinc-deficient rabbits.
Lipopolysaccharide (LPS) was used to induce maternal hypozincemia in order to test the hypothesis that altered zinc homeostasis is developmentally toxic in the rabbit. Treatment of dams on Gestation Day (GD) 8 with LPS (0.67 microgram/kg i.v.) caused total resorption of 78% (7 of 9) of the litters whereas GD 10 treatment increased the percentage of resorbed implantations (18-fold), but resulted in only 14% (1 of 7) totally resorbed litters. Cotreatment with zinc oxide (ZnO) on GD 10 decreased the resorption rate by 44%, indicating that hypozincemia was partially responsible for the resorptions. However, ZnO had no effect on resorption rate in GD 8 LPS-treated dams. No malformations were observed with LPS dosing on either gestation day. To determine whether LPS-induced Zn deficiency had any direct effects on rabbit embryos, normal GD 9 embryos were cultured for 48 h in serum from LPS-treated dams (0.53 +/- 0.01 microgram/mL Zn) or from controls (1.74 +/- 0.07 micrograms/mL Zn). Embryo growth and development were normal in both groups, indicating a lack of any direct embryo effects of Zn deficiency. Finally, maternal plasma progesterone and the Zn content of conceptus tissues were measured 24 h after LPS injection on GD 10. Despite a marked decrease in maternal serum Zn, no significant changes in embryo, visceral yolk sac, yolk sac cavity-exoceolomic fluid, or placental Zn were found. However, maternal progesterone levels were decreased 33 and 28% in the LPS and LPS + ZnO groups, respectively. Taken together, these results indicate that rabbits may differ from rodent species in their lesser susceptibility to the teratogenic potential of transient maternal Zn deficiency, as well as in their resistance to conceptus Zn changes. Nonetheless, Zn deficiency may be responsible for an increase in resorption rate in the rabbit.
Pitt
J A
JA
Developmental and Reproductive Toxicology, Health and Environmental Research Laboratory, Dow Chemical Company, Midland, Michigan 48674, USA.
Zoellner
M J
MJ
Carney
E W
EW
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D020964:Embryo Loss / Q000139:chemically induced* / Q000517:prevention & control; D004622:Embryo, Mammalian / Q000187:drug effects*; D004926:Escherichia coli; D005260:Female; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008668:Metallothionein / Q000096:biosynthesis*; D011247:Pregnancy; D011817:Rabbits; D015032:Zinc / Q000172:deficiency*; D015034:Zinc Oxide / Q000627:therapeutic use
D008070:Lipopolysaccharides; D008668:Metallothionein; D015032:Zinc; D015034:Zinc Oxide