title: Increased Fetal Thymocytes Apoptosis Contributes to Prenatal Nicotine Exposure-induced Th1/Th2 Imbalance in Male Offspring Mice.
abstract: Nicotine, a definite risk factor during pregnancy, is an immunomodulator. This study was designed to investigate the effects of prenatal nicotine exposure (PNE) on the balance of Th1/Th2 in offspring, and further explore the developmental origin mechanisms from the perspective of fetal thymocytes apoptosis. Pregnant Balb/c mice were administered 1.5 mg/kg nicotine subcutaneously twice per day from gestational day (GD) 9 to GD18. Results showed that PNE could cause a Th2 shift in male offspring, manifested as increased ratio of IgG1/IgG2a, IL-4 production in serum, and IL-4/IFN-γ expression ratio in spleen. Increased apoptosis of total thymocytes and CD4SP and reduced cell proportion of CD4SP were found in PNE male offspring on postnatal day (PND) 14 and PND 49. In the fetuses, decreased body weight and organ index of fetal thymus, histological changes in fetal thymus, reduced CD4SP proportion and increased fetal thymocyte apoptosis were observed in nicotine group. The increased mRNA expression of genes involved in Fas-mediated apoptotic pathway and protein expression of Fas were also detected. In conclusion, PNE could cause a Th2 shift in male offspring mediated by reduced CD4+T cells output, which may result from the increasing apoptosis of total thymocytes and CD4SP.
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: You-E
authors.initials: YE
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Han-Xiao
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Hou
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Qu
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ping
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005333:Fetus / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D060168:Thymocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D009538:Nicotine