title: Effect of microcystin-LR on human placental villous trophoblast differentiation in vitro.
abstract: Microcystin-LR is a cyanobacterial toxin found in surface and recreational waters that inhibits protein phosphatases and may disrupt the cytoskeleton. Microcystins induce apoptosis in hepatocytes at ≤ 2.0 µM. Nothing is known about the effects of microcystins on human placental trophoblast differentiation and function. The differentiation of villous trophoblasts to form syncytiotrophoblast occurs throughout pregnancy and is essential for normal placental and fetal development. To investigate the effects of microcystin, villous cytotrophoblasts were isolated from term placentas using an established method and exposed to microcystin-LR. Microcystin-LR below the cytotoxic dose of 25 µM did not cause cell rounding or detachment, had no effect on apoptosis, and no effect on the morphological differentiation of mononucleated cytotrophoblasts to multinucleated syncytiotrophoblast. However, secretion of human chorionic gonadotropin (hCG) increased in a microcystin-LR dose-dependent manner. When incubated with l-buthionine sulphoximine (BSO) to deplete glutathione levels, trophoblast morphological differentiation proceeded normally in the presence of microcystin-LR. Microcystin-LR did not disrupt the trophoblast microtubule cytoskeleton, which is known to play a role in trophoblast differentiation. Immunofluorescence studies showed that trophoblasts express organic anion transport protein 1B3 (OATP1B3), a known microcystin transport protein. In comparison to hepatocytes, trophoblasts appear to be more resistant to the toxic effects of microcystin-LR. The physiological implications of increased hCG secretion in response to microcystin-LR exposure remain to be determined.
authors.affiliation: Department of Cell Biology and Human Anatomy, School of Medicine, University of California Davis, Davis, California, USA.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Douglas
authors.affiliation: Department of Cell Biology and Human Anatomy, School of Medicine, University of California Davis, Davis, California, USA.
authors.forename: Twanda L
authors.initials: TL
authors.lastname: Thirkill
authors.affiliation: Department of Cell Biology and Human Anatomy, School of Medicine, University of California Davis, Davis, California, USA.
authors.forename: Priyadarsini
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Cell Biology and Human Anatomy, School of Medicine, University of California Davis, Davis, California, USA.
authors.forename: Minerva
authors.initials: M
authors.lastname: Loi
authors.affiliation: Office of Research and Development, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Hilborn
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D006801:Humans; D008387:Marine Toxins / Q000633:toxicity*; D052998:Microcystins / Q000633:toxicity*; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D006063:Chorionic Gonadotropin; D008387:Marine Toxins; D052998:Microcystins; C057862:cyanoginosin LR
keywords: human; human chorionic gonadotropin; in vitro; microcystin; placenta