Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect

Abstract

LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown–rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

Maternal LPS Exposure during Pregnancy Impairs Testicular Development, Steroidogenesis and Spermatogenesis in Male Offspring

“…Maternal LPS exposure during the second trimester caused fetal death and preterm delivery [8]. We and others found that maternal LPS exposure during the third trimester led to fetal death, fetal growth restriction, skeletal development retardation, and preterm labor [9]–[13]. Several studies including ours showed that maternal LPS exposure resulted in fetal teratogenesis in rats [14], mice [15], [16], and golden hamsters [17].…”

Diselementosis as a risk factor of embryo loss in lactating cows

“…Therefore, developmental delay and embryo death in dairy cows at early gestation stages are the consequences of zinc deficiency and disorders of its metabolism in the organism. Experiment in vivo (19) showed that additional introduction of zinc to animals effectively protected them from lipopolysaccharide-induced intrauterine growth restriction and embryo and fetus death.…”

Prenatal zinc supplementation to lipopolysaccharide infected female rats prevents neurochemical, behavioral and biochemical deficits produced in infants

“…[37] Recent studies showed that ZnSO 4 supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect. [28] Nevertheless, the molecular mechanism of zinc-mediated protection against LPS induced developmental toxicity remains elusive. Present study was designed to investigate the gender biased effects of LPS injection during d14-17 of pregnancy on the neurobehavioral, biochemical and histopathological parameters in off-springs.…”

“…[27] Increasing evidence demonstrates that zinc has an anti-inflammatory effect. [28] A recent study found that subcutaneous injection with zinc sulfate alleviated LPSinduced neurodevelopmental damage in fetal brain. [29,30] Zinc is capable of inhibiting LPS or IL-1β-induced nitric oxide (NO) formation as well as NO formation by NO synthase (NOS).…”