title: Megalin Is Predominantly Observed in Vesicular Structures in First and Third Trimester Cytotrophoblasts of the Human Placenta.
abstract: The membrane receptor megalin is crucial for normal fetal development. Besides its expression in the developing fetus, megalin is also expressed in the human placenta. Similar to its established function in the kidney proximal tubules, placental megalin has been proposed to mediate uptake of vital nutrients. However, details of megalin expression, subcellular localization, and function in the human placenta remain to be established. By immunohistochemical analyses of first trimester and term human placenta, we showed that megalin is predominantly expressed in cytotrophoblasts, the highly proliferative cells in placenta. Only limited amounts of megalin could be detected in syncytiotrophoblasts and least in term placenta syncytiotrophoblasts. Immunocytochemical analyses furthermore showed that placental megalin associates with structures of the endolysosomal apparatus. Combined, our results clearly place placental megalin in the context of endocytosis and trafficking of ligands. However, due to the limited expression of megalin in syncytiotrophoblasts, especially in term placenta, it appears that the main role for placental megalin is not to mediate uptake of nutrients from the maternal bloodstream, as previously proposed. In contrast, our results point toward novel and complex functions for megalin in the cytotrophoblasts. Thus, we propose that the perception of placental megalin localization and function should be revised.
authors: Department of Biomedicine, Aarhus University, Aarhus C, Denmark (TS, EIC, JNC, TK, AL, BH, MM).
authors: Tina
authors: T
authors: Storm
authors: Department of Biomedicine, Aarhus University, Aarhus C, Denmark (TS, EIC, JNC, TK, AL, BH, MM).
authors: Erik I
authors: EI
authors: Christensen
authors: Department of Biomedicine, Aarhus University, Aarhus C, Denmark (TS, EIC, JNC, TK, AL, BH, MM).
authors: Julie Nelly
authors: JN
authors: Christensen
authors: Department of Biomedicine, Aarhus University, Aarhus C, Denmark (TS, EIC, JNC, TK, AL, BH, MM).
authors: Tine
authors: T
authors: Kjaergaard
authors: Department of Clinical Medicine-Obstetrics and Gynaecology, Aarhus University Hospital, Skejby, Denmark (NU).
authors: Niels
authors: N
authors: Uldbjerg
authors: Department of Biomedicine, Aarhus University, Aarhus C, Denmark (TS, EIC, JNC, TK, AL, BH, MM).
authors: Agnete
authors: A
authors: Larsen
authors: Department of Biomedicine, Aarhus University, Aarhus C, Denmark (TS, EIC, JNC, TK, AL, BH, MM).
authors: Bent
authors: B
authors: Honoré
authors: Mette
authors: M
authors: Madsen
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2
keywords: cytotrophoblast; endocytosis; endolysosomal system; growth factor signaling; megalin; placenta; syncytiotrophoblast; transmembrane receptor