Melatonin protects against lipopolysaccharide-induced intra-uterine fetal death and growth retardation in mice.
Lipopolysaccharide (LPS) has been associated with adverse developmental outcomes, including intra-uterine fetal death (IUFD) and intra-uterine growth retardation (IUGR). However, the exact mechanism for LPS-induced IUFD and IURD remains unclear. LPS stimulates macrophages to generate reactive oxygen species (ROS). Therefore, we hypothesize that ROS may be involved in LPS-induced IUFD and IURD. Melatonin is a powerful endogenous antioxidant. In this study, we investigated the protective effects of melatonin on LPS-induced IUFD and IURD in ICR mice. All pregnant mice except controls received an intraperitoneal (75 microg/kg, i.p.) injection of LPS on gestational day (gd) 15-17. The experiment was carried out in two different modes. In mode A, the pregnant mice received two doses of melatonin within 24 hr, one (5 or 10 mg/kg) injected immediately after LPS and the other (5 or 10 mg/kg) injected at 3 hr after LPS. In mode B, the pregnant mice were pretreated with 10 mg/kg of melatonin 18 hr before LPS and then received two doses of melatonin in 24 hr, one (10 mg/kg) injected immediately after LPS and the other (10 mg/kg) injected 3 hr after LPS. The number of live fetuses, dead fetuses and resorption sites were counted on gd 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Results showed that post-treatments with melatonin significantly attenuated LPS-induced IUFD in a dose-dependent manner. Surprisingly, pre- plus post-treatments with melatonin almost blocked LPS-induced IUFD. In addition, both post-treatments and pre- plus post-treatments with melatonin significantly alleviated LPS-induced decreases in crown-rump and tail lengths and reversed LPS-induced skeletal developmental retardation. However, melatonin had little effect on LPS-induced decrease in fetal weight. Furthermore, pre- plus post-treatments with melatonin significantly attenuated LPS-induced lipid peroxidation in maternal liver. These results indicate that melatonin protects against LPS-induced IURD and IUGR via counteracting LPS-induced oxidative stress.
Chen
Yuan-Hua
YH
Department of Toxicology, Anhui Medical University, Hefei, China.
Xu
De-Xiang
DX
Wang
Jian-Ping
JP
Wang
Hua
H
Wei
Ling-Zhen
LZ
Sun
Mei-Fang
MF
Wei
Wei
W
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology; D005260:Female; D005313:Fetal Death / Q000517:prevention & control*; D005317:Fetal Growth Retardation / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D008070:Lipopolysaccharides; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D008550:Melatonin