Transplacental transfer and biotransformation studies of nicotine in the human placental cotyledon perfused in vitro

Pastrakuljic, Aleksandra; Schwartz, Robert; Simone, Carmine; Derewlany, Lidia O.; Knie, Brenda; Koren, Gideon

doi:10.1016/s0024-3205(98)00522-0

Cited by 83 publications

(55 citation statements)

References 14 publications

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“…nicotine), implying that the function of the cholinergic system in the developing embryo can be influenced by maternal smoking. Indeed, the placenta does not pose a metabolic barrier to nicotine transfer from the mother (Pastrakuljic et al, 1998), and therefore nicotine can readily cross through the placenta and accumulate in utero (Luck et al, 1985). In addition, the expression of nicotine-metabolizing enzymes appears either near birth (CYP2B) or 2 week postpartum (CYP2A) (Nagata et al, 2003;Rich and Boobies, 1997).…”

Section: Discussionmentioning

confidence: 99%

The cholinergic system is involved in regulation of the development of the hematopoietic system

et al. 2007

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Gene expression profiling demonstrated that components of the cholinergic system, including choline acetyltransferase, acetylcholinesterase and nicotinic acetylcholine receptors (nAChRs), are expressed in embryonic stem cells and differentiating embryoid bodies (EBs). Triggering of nAChRs expressed in EBs by nicotine resulted in activation of MAPK and shifts of spontaneous differentiation toward hemangioblast. In vivo, non-neural nAChRs are detected early during development in fetal sites of hematopoiesis. Similarly, in vivo exposure of the developing embryo to nicotine resulted in higher numbers of hematopoietic progenitors in fetal liver. However postpartum, the number of hematopoietic stem/progenitor cells (HSPC) was decreased, suggesting an impaired colonization of the fetal bone marrow with HSPCs. This correlated with increased number of circulating HSPC and decreased expression of CXCR4 that mediates migration of circulating cells into the bone marrow regulatory niche. In addition, protein microarrays demonstrated that nicotine changed the profile of cytokines produced in the niche. While the levels of IL1α, IL1β, IL2, IL9 and IL10 were not changed, the production of hematopoiesis-supportive cytokines including G-CSF, GM-CSF, IL3, IL6 and IGFBP-3 was decreased. This correlated with the decreased repopulating ability of HSPC in vivo and diminished hematopoietic activity in bone marrow cultures treated with nicotine. Interestingly, nicotine stimulated the production of IL4 and IL5, implying a possible role of the cholinergic system in pathogenesis of allergic diseases. Our data provide evidence that the nicotine-induced imbalance of the cholinergic system during gestation interferes with normal development and provides the basis for negative health outcomes postpartum in active and passive smokers.

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Section: Discussionmentioning

confidence: 99%

The cholinergic system is involved in regulation of the development of the hematopoietic system

et al. 2007

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“…Nicotine also accumulates in breast milk (milk/plasma ratio 2.9) (Luck and Nau, 1984;Dahlstrom et al, 1990). Nicotine crosses the placental barrier easily, and there is evidence for the accumulation of nicotine in fetal serum and amnionic fluid in slightly higher concentrations than in maternal serum (Luck et al, 1985;Pastrakuljic et al, 1998;Dempsey and Benowitz, 2001).…”

mentioning

confidence: 99%

Metabolism and Disposition Kinetics of Nicotine

2005

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“…Active transport of nicotine across the placenta could produce this result, and some evidence for active transport exists in a choriocarcinoma cell line [28], but the transfer of nicotine across the perfused ex-vivo placenta is similar to that of antipyrine and most readily explained by passive diffusion [29,30]. Possibly the small amount of Nic311 crossing the placenta was sufficient to bind and retain nicotine in the fetus, effectively opposing any effect of maternal Nic311 to decrease nicotine transfer to the fetus.…”

Section: Discussionmentioning

confidence: 99%

Changes in maternal and fetal nicotine distribution after maternal administration of monoclonal nicotine-specific antibody to rats

Keyler

LeSage

Dufek

et al. 2006

International Immunopharmacology

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Vaccination against nicotine to elicit the production of nicotine-specific antibodies is a potential treatment for tobacco addiction which reduces nicotine distribution from serum to brain. Vaccination of pregnant rats also reduces the distribution of maternally-administered nicotine to fetal brain. Whether this is due to maternal antibody reducing the transfer of nicotine from mother to fetus, or to fetal antibody altering the distribution of nicotine within the fetus, is not clear. In the current study, passive immunization of rats with the murine monoclonal nicotine-specific antibody Nic311 was used as a surrogate for vaccination because antibody transfer to the fetus was anticipated to be lower than with vaccination. Pregnant rats received nicotine from gestational day (GD) 18-20 as frequent i.v. boluses to simulate nicotine exposure from smoking. Nic 311 was administered at doses of 30, 80 or 240 mg/kg on GD19. Fetal serum Nic311 levels on GD20 were <3% of concurrent maternal levels, but concentrations of up to 20 ug/ml in fetal serum were obtained owing to the very high levels in maternal serum. Accumulation of the chronically administered nicotine, measured on GD20, was not changed by Nic311 treatment in either maternal or fetal brain. The early distribution of nicotine to maternal brain, measured 5 min after a dose, was markedly reduced by Nic311, while the early distribution of nicotine to whole fetus and fetal brain was not substantially altered.. These data suggest that the limited transfer of Nic311 to the fetus in turn limits the ability of Nic311 to reduce nicotine distribution to fetal brain.

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Transplacental transfer and biotransformation studies of nicotine in the human placental cotyledon perfused in vitro

Cited by 83 publications

References 14 publications

The cholinergic system is involved in regulation of the development of the hematopoietic system

The cholinergic system is involved in regulation of the development of the hematopoietic system

Metabolism and Disposition Kinetics of Nicotine

Changes in maternal and fetal nicotine distribution after maternal administration of monoclonal nicotine-specific antibody to rats

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