title: Maternal-fetal transfer of selenium in the mouse.
abstract: Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.
authors: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. raymond.burk@vanderbilt.edu
authors: Raymond F
authors: RF
authors: Burk
authors: Gary E
authors: GE
authors: Olson
authors: Kristina E
authors: KE
authors: Hill
authors: Virginia P
authors: VP
authors: Winfrey
authors: Amy K
authors: AK
authors: Motley
authors: Suguru
authors: S
authors: Kurokawa
mesh_terms: D000818:Animals; D001692:Biological Transport; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010920:Placenta / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D012643:Selenium / Q000378:metabolism*; D051149:Selenoprotein P / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015017:Yolk Sac / Q000196:embryology / Q000378:metabolism
chemical_list: D026502:LDL-Receptor Related Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D051149:Selenoprotein P; C098773:low density lipoprotein receptor-related protein 8; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase; D012643:Selenium
keywords: apolipoprotein E receptor-2; glutathione peroxidase-3; placenta; selenoprotein P; visceral yolk sac
references: J Biol Chem. 2004 Aug 13;279(33):34302-10
references: 15180987
references: Life Sci. 2009 Jun 19;84(25-26):888-93
references: 19389411
references: Biochim Biophys Acta. 2009 Nov;1790(11):1441-7
references: 19345254
references: J Nutr. 2004 Jan;134(1):157-61
references: 14704310
references: J Neurosci. 2011 Oct 5;31(40):14413-23
references: 21976526
references: Placenta. 2006 Jun-Jul;27(6-7):550-9
references: 16129486
references: J Assoc Off Anal Chem. 1983 Jul;66(4):918-26
references: 6885699
references: Am J Physiol Renal Physiol. 2010 May;298(5):F1244-53
references: 20015939
references: J Biol Chem. 2007 Apr 20;282(16):12290-7
references: 17314095
references: J Biol Chem. 2002 Apr 12;277(15):12749-54
references: 11821412
references: Am J Physiol Gastrointest Liver Physiol. 2011 Jul;301(1):G32-8
references: 21493731
references: J Biol Chem. 2012 Aug 17;287(34):28717-26
references: 22761431
references: Clin Chem. 1990 Dec;36(12):2124-6
references: 2253359
references: Am J Pathol. 1992 Jan;140(1):33-44
references: 1731529
references: Proc Natl Acad Sci U S A. 1997 May 27;94(11):5531-4
references: 9159106
references: J Neurosci. 2007 Jun 6;27(23):6207-11
references: 17553992
references: J Biol Chem. 1996 Apr 5;271(14):8373-80
references: 8626535
references: J Biol Chem. 2008 Mar 14;283(11):6854-60
references: 18174160
references: Biochim Biophys Acta. 2006 Dec;1760(12):1789-93
references: 17014962
references: J Biol Chem. 2003 Apr 18;278(16):13640-6
references: 12574155
references: J Biol Chem. 2007 Apr 13;282(15):10972-80
references: 17311913
references: Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8460-4
references: 8710893
references: J Biol Chem. 2012 Nov 23;287(48):40414-24
references: 23038251
references: Biochem Biophys Res Commun. 1976 Aug 23;71(4):952-8
references: 971321