Zinc treatment prevents lipopolysaccharide‐induced teratogenicity in mice

Abstract

The findings of this study strongly support the hypothesis that LPS teratogenicity is mediated at least in part by MT-induced changes in maternal Zn homeostasis,which compromises fetal Zn supply.

Dietary Zinc Supplementation Ameliorates LPS-Induced Teratogenicity in Mice

“…Pregnant mice treated with alcohol and LPS (14,28) presented with abnormalities similar to those observed in rodents fed Zndeficient diet (Յ1 mg Zn/kg diet) throughout pregnancy (29 -31). The observed abnormalities include craniofacial, neural tube, and limb bud defects (14,28 -31).…”

“…Therefore, this change in plasma Zn pool can be likened to a transient fetal Zn deficiency with deleterious effects on the fetus. The involvement of MT in this process can be seen in studies where MT -/-(MT-1 and -2 knockout) mice exposed to alcohol or LPS on GD8 had fetuses that were morphologically unaffected by these teratogens (14,28). Our laboratory (14) has demonstrated that a single intraperitoneal injection of LPS increased liver MT by 30-fold basal from 6 to 24 h, which coincided with an 80% decrease in plasma Zn over the same time period.…”

“…The involvement of MT in this process can be seen in studies where MT -/-(MT-1 and -2 knockout) mice exposed to alcohol or LPS on GD8 had fetuses that were morphologically unaffected by these teratogens (14,28). Our laboratory (14) has demonstrated that a single intraperitoneal injection of LPS increased liver MT by 30-fold basal from 6 to 24 h, which coincided with an 80% decrease in plasma Zn over the same time period. Moreover, in other studies where we induced MT with alcohol, not only was there a reduced transfer of Zn to the fetus but whole-fetus Zn concentration was significantly less (25).…”

“…Endotoxin was also found to occur in higher concentrations in women with BV (11). Previous studies in rodents have shown that administration of high intravenous doses (Ͼ10 mg/100 kg body weight) of LPS on GD8 caused 100% resorption of implantation sites (12), whereas lower dosing regimes led to development of fetal malformations involving the eye, brain (13), neural crest defects, cleft palate, and limb anomalies (12,14). In contrast, when LPS was given to mice subcutaneously later in gestation (GD13), fetuses that were not resorbed were phenotypically normal (15).…”

“…This is perhaps not surprising inasmuch as the time of exposure was outside the critical window of organogenesis (GD8 -12 in mice). Recently, work from our laboratory (14) has found a mechanistic explanation for LPS teratogenicity whereby MT is the key mediator.…”