title: Exposure to nicotine during gestation interferes with the colonization of fetal bone marrow by hematopoietic stem/progenitor cells.
abstract: Environmental factors, including cigarette smoke components, can cross the placental barrier and accumulate in amniotic fluid and fetal tissue, and, therefore, interfere with the normal course of ontogenesis. Although cigarette smoke contains numerous compounds, the most adverse effects on mammalian tissues have been associated with nicotine. The aim of this study was to investigate the effect of intrauterine exposure to nicotine on hematopoiesis during fetal development and postpartum. Intrauterine exposure of mice to nicotine resulted in a more than two-fold reduction of the delayed- type hypersensitivity (DTH) response and a 2.5-fold decrease in the number of plaque forming cell (PFC) in offspring after 1 month of postnatal life, and correlated with low counts of mature lymphocytes and lymphoid progenitors in hematopoietic tissues. Neonates exposed to nicotine during gestation showed a significant decrease in the number of bone marrow hematopoietic progenitors, as measured by colony-forming unit (CFU) and long-term culture initiating cell (LTC-IC) assays, and decreased concentration of interleukin-6 (IL-6) in their serum. Analysis of the fetal bone marrow (E15) obtained from nicotine-exposed fetuses demonstrated a lower number of hematopoietic progenitors, whereas their number in the fetal liver was not significantly changed. Our data provide evidence that by targeting the nicotinic acetylcholine receptor (nAChR) nicotine interferes with the fetal development of the hematopoietic system. Inferior colonization of the fetal bone marrow by hematopoietic stem/progenitor cells (HSPC) subsequently results in an imbalance of mature blood and immune cell production after birth.
authors.affiliation: La Jolla Institute for Molecular Medicine, Division of Vascular Biology, San Diego, CA 92121, USA.
authors.forename: Naira
authors.initials: N
authors.lastname: Serobyan
authors.forename: Irina
authors.initials: I
authors.lastname: Orlovskaya
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kozlov
authors.forename: Sophia K
authors.initials: SK
authors.lastname: Khaldoyanidi
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000196:embryology; D001854:Bone Marrow Cells / Q000166:cytology; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus / Q000166:cytology / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D007107:Immune System / Q000187:drug effects / Q000196:embryology; D015850:Interleukin-6 / Q000172:deficiency; D008431:Maternal-Fetal Exchange; D051379:Mice; D009538:Nicotine / Q000009:adverse effects*; D011247:Pregnancy
chemical_list: D015850:Interleukin-6; D009538:Nicotine