IN-VIVO AND IN-VITRO DEVELOPMENTAL TOXICITY IN LPS-INDUCED ZINC-DEFICIENT RABBITS

Lipopolysaccharide (LPS) was used to induce maternal hypozincemia in o rder to test the hypothesis that altered zinc homeostasis is developme ntally toxic in the rabbit, Treatment of dams on Gestation Day (GD) 8 with LPS (0.67 mu g/kg i.v.) caused total resorption of 78% (7 of 9) o f the litters whereas GD 10 treatment increased the percentage of reso rbed implantations (IS-fold), but resulted in only 14% (1 of 7) totall y resorbed litters, Cotreatment with zinc oxide (ZnO) on GD 10 decreas ed the resorption rate by 44%, indicating that hypozincemia was partia lly responsible for the resorptions, However, ZnO had no effect on res orption rate in GD 8 LPS-treated dams, No malformations were observed with LPS dosing on either gestation day. To determine whether LPS-indu ced 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 mu g/mL Zn) or from controls (1.74 +/- 0.07 mu g/mL Zn), Embr yo growth and development were normal in both groups, indicating a lac k of any direct embryo effects of Zn deficiency, Finally, maternal pla sma progesterone and the Zn content of conceptus tissues were measured 24 h after LPS injection on GD 10, Despite a marked decrease in mater nal serum Zn, no significant changes in embryo, visceral yolk sac, yol k sac cavity-exoceolomic fluid, or placental Zn were found, However, m aternal progesterone levels were decreased 33 and 28% in the LPS and L PS + ZnO groups, respectively. Taken together, these results indicate that rabbits may differ from rodent species in their lesser susceptibi lity 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. (C) 1997 Elsevier Science Inc.