Reactive Oxygen Species Contribute to Lipopolysaccharide-Induced Teratogenesis in Mice

Abstract

Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including embryonic resorption, fetal death and growth retardation, and preterm delivery. In the present study, we showed that an ip injection with LPS daily from gestational day (gd) 8 to gd 12 resulted in the incidence of external malformations. The highest incidence of malformed fetuses was observed in fetuses from dams exposed to 20 microg/kg LPS, in which 34.9% of fetuses per litter were externally malformed. In addition, 17.4% of fetuses per litter in 30 microg/kg group and 12.5% of fetuses per litter in 10 microg/kg group were externally malformed. Importantly, external malformations were also observed in fetuses from dams exposed to only two doses of LPS (20 microg/kg, ip) on gd 8, in which 76.5% (13/17) of litters and 39.1% of fetuses per litter were affected. LPS-induced teratogenicity seemed to be associated with oxidative stress in fetal environment, measured by lipid peroxidation, nitrotyrosine residues, and glutathione (GSH) depletion in maternal liver, embryo, and placenta. alpha-Phenyl-N-t-butylnitrone (PBN, 100 mg/kg, ip), a free radical spin-trapping agent, abolished LPS-induced lipid peroxidation, nitrotyrosine residues, and GSH depletion. Consistent with its antioxidant effects, PBN decreased the incidence of external malformations. Taken together, these results suggest that reactive oxygen species might be, at least partially, involved in LPS-induced teratogenesis.

Reactive Oxygen Species-Triggered Trophoblast Apoptosis Is Initiated by Endoplasmic Reticulum Stress via Activation of Caspase-12, CHOP, and the JNK Pathway in Toxoplasma gondii Infection in Mice

“…On the one hand, redox-sensitive signal transduction pathways are critical for developmental processes, including proliferation, differentiation, and apoptosis of human tissues, especially for placenta; on the other hand, teratogens that induce oxidative stress, such as chemical poisoning and infection, may induce teratogenesis via the misregulation of the above-mentioned pathways (46). In particular, previous studies have discovered that ROS were involved in teratogenic processes in mice treated with LPS (7,50), which is one well-recognized pathogen-associated molecular pattern (PAMP) of Gram-negative bacteria. Structures analogous to LPS have been found in T. gondii, such as glycosylphosphatidylinositols (GPI) (9,36).…”

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

“…Several earlier studies showed that maternal LPS exposure resulted in the development of malformed fetuses in rats and golden hamsters (8)(9)(10). Recently, we showed that maternal LPS exposure from gestational day (GD) 8 to GD12 caused external malformations and skeletal abnormalities in mice (11). We and others found that maternal LPS exposure at late gestational stages led to fetal death, intrauterine growth restriction (IUGR), skeletal development retardation, and preterm delivery (12)(13)(14)(15)(16).…”

Urogenital endogenous bacterial infection and systemic enzymotherapy

“…В опытах продемонстри-ровано, что интраамниотическое введение ЛПС влечет за собой тяжелые последствия как для материнского организма, способствуя развитию хорионамнионита, так и для плода, вызывая повреждения центральной нерв-ной системы и формирование врожденных пороков и аномалий [33,34].…”

“…В связи с вероятностью формирования при эндоген-ной инфекции связанных с беременностью нарушений в системе гемостаза [27,[30][31][32][33][34], особое значение приоб-ретают эффекты энзимов на свертывающую систему крови. На сегодня доказаны их следующие эффекты: 1) снижение (нормализация) процессов агрегации тром-боцитов и эритроцитов, что обусловлено снижением концентрации тромбоксана и блокированием адгезив-ных молекул; 2) снижение концентрации провоспа-лительных белков (брадикинина, фибриногена) и др.…”