The Effect Of Nicotine On Intrauterine Fetal Blood Oxidation Status And Impairment Development Of Central Cholinergic System

Objective To explore the effect of nicotine on intrauterine fetal blood oxidation during different gestation period,and influence on mRNAs expression of ChAT, VACHT, CHT1, muscarinic receptors in brain.Methods 1. Subcutaneously injection of nicotine 3mg/kg/day was employed during different gestation period(GD3-21, GD8-21, GD15-21), maternal and fetal blood samples were detected for blood values.2. Placent weight ,fetal brain and body weight were measured for intrauterine growth retardation.3.Real-time quantitative polymerase reaction assay was established and performed to measure mRNA of cholinergic markers- ChAT,VACHT,CHT1 and M1, M2, M3, M4 mRNAs in the fetal brain.4. Immunohistochemistry was used for determining M2, M3 protein.Result 1. Under condition of maternal exposure to nicotine, fetal blood PO2 was lowered and PCO2 was enhanced associated with a significant increase of lactic acid, hemoglobin, and hematocrit. Fetal blood pH,fetal body brain weight were reduced, while fetal Na~+, K~+, plasma osmolality, and blood glucose were not changed.2. Subcutaneous administration of nicotine in maternal rats during pregnancy also suppressed ChAT, VAChT, CHT1 and M1, M2, M3, M4 mRNAs in the fetal brain. 3.Nicotine-affected fetal hypoxic responses and the cholinergic marker expression were more severe when nicotine was used from the early gestation.Conclusion 1.Nicotine-induced fetal problems including hypoxia and abnormal development is related to when and how long exposure of nicotin during pregnancy.2. Maternal nicotine in pregnancy could cause deficits of ChAT, VAChT, CHT1 and M1, M2,M3,M4 in the fetal brain.3. The results provide new information for mechanisms of fetal growth restriction in utero and poor development of the central nervous systems by exposure to nicotine in utero.