Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect.
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.
Department of Toxicology, Anhui Medical University, Hefei 230032, China.
Yuan-Hua
YH
Chen
Mei
M
Zhao
Xue
X
Chen
Ying
Y
Zhang
Hua
H
Wang
Ying-Ying
YY
Huang
Zhen
Z
Wang
Zhi-Hui
ZH
Zhang
Cheng
C
Zhang
De-Xiang
DX
Xu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D019587:Dietary Supplements / Q000706:statistics & numerical data; D005260:Female; D005313:Fetal Death / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005317:Fetal Growth Retardation / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D005323:Fetal Monitoring / Q000379:methods / Q000401:mortality; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D047928:Premature Birth / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D011897:Random Allocation; D015032:Zinc / Q000008:administration & dosage* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D015032:Zinc