Pitt J A, Zoellner M J, Carney E W
Developmental and Reproductive Toxicology, Health and Environmental Research Laboratory, Dow Chemical Company, Midland, Michigan 48674, USA.
Reprod Toxicol. 1997 Nov-Dec;11(6):771-9. doi: 10.1016/s0890-6238(97)00060-9.
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.
使用脂多糖（LPS）诱导母体低锌血症，以检验锌稳态改变对家兔发育具有毒性这一假说。在妊娠第8天（GD8）给母兔静脉注射LPS（0.67微克/千克），导致78%（9窝中的7窝）的仔兔全部吸收，而在GD10进行处理则增加了吸收着床的百分比（增加了18倍），但仅导致14%（7窝中的1窝）的仔兔全部吸收。在GD10同时给予氧化锌（ZnO）可使吸收率降低44%，这表明低锌血症是吸收的部分原因。然而，ZnO对GD8接受LPS处理的母兔的吸收率没有影响。在任何一个妊娠日给予LPS均未观察到畸形。为了确定LPS诱导的锌缺乏是否对家兔胚胎有任何直接影响，将正常的GD9胚胎在来自LPS处理母兔（锌含量为0.53±0.01微克/毫升）或对照母兔（锌含量为1.74±0.07微克/毫升）的血清中培养48小时。两组胚胎的生长和发育均正常，这表明锌缺乏对胚胎没有任何直接影响。最后，在GD10注射LPS后24小时测量母体血浆孕酮和胚胎组织的锌含量。尽管母体血清锌显著降低，但未发现胚胎、内脏卵黄囊、卵黄囊腔-外体腔液或胎盘锌有显著变化。然而，LPS组和LPS+ZnO组的母体孕酮水平分别降低了33%和28%。综上所述，这些结果表明，家兔对短暂母体锌缺乏的致畸潜力的易感性较低，以及对胚胎锌变化的抵抗力可能与啮齿动物不同。尽管如此，锌缺乏可能是家兔吸收率增加的原因。
