Nicotine downregulates the l-selectin system that mediates cytotrophoblast emigration from cell columns and attachment to the uterine wall.
Here we show that maternal smoking downregulated, in a dose-dependent manner, cytotrophoblast expression of l-selectin and its TRA-1-81-reactive carbohydrate ligands. Cell islands -- cell columns that fail to make uterine attachments, often more numerous in the placentas of smokers -- exhibited an even greater downregulation of the l-selectin adhesion system. These effects were attributable to nicotine, since exposure of explanted villi to this drug in vitro reproduced the effects observed in situ. Videomicroscopy showed that the downstream consequences included inhibition of all stages of cytotrophoblast outgrowth from columns, including rolling adhesion within columns and generation of invasive cells at the distal ends. These results suggest that nicotine, acting through the l-selectin adhesion system, impairs the development of cell columns that connect the fetal portion of the placenta to the uterus, one possible reason why women who smoke have a much harder time achieving and sustaining pregnancy than their nonsmoking counterparts.
Zdravkovic
Tamara
T
Department of Cell and Tissue Biology, University of California, San Francisco, CA 94143, USA.
Genbacev
Olga
O
Prakobphol
Akraporn
A
Cvetkovic
Milos
M
Schanz
Andrea
A
McMaster
Michael
M
Fisher
Susan J
SJ
D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002582:Cervix Mucus / Q000737:chemistry / Q000187:drug effects; D002824:Chorionic Villi / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006801:Humans; D007632:Keratan Sulfate / Q000276:immunology; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D009538:Nicotine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014599:Uterus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005731:Ganglionic Stimulants; D008024:Ligands; D019041:L-Selectin; D009538:Nicotine; D007632:Keratan Sulfate