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Effect of Microcystin-LR on human placental villous trophoblast differentiation in vitro
Citation:
Douglas, G., T. Thirkill, P. Kumar, M. Loi, AND E Hilborn. Effect of Microcystin-LR on human placental villous trophoblast differentiation in vitro. ENVIRONMENTAL TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 31(4):427-39, (2016).
Impact/Purpose:
Cyanobacteria and their toxins (cyanotoxins) are unregulated contaminants, although selected cyanotoxins are included in the Safe Drinking Water Act’s Contaminant Candidate List. Microcystin, a CCL cyanotoxin, is a cyanobacteria toxin occurs worldwide and have been associated with adverse health effects among wildlife, livestock, companion animal species and uncommonly people. This is the first report to document the potential for female reproductive health effects associated with microcystin exposure.
Description:
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 fetaldevelopment. 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-buthioninesulphoximine (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 physiologicalimplications of increased hCG secretion in response to microcystin-LR exposure remain to be determined.
