title: Expression and role of cubilin in the internalization of nutrients during the peri-implantation development of the rodent embryo.
abstract: Histiotrophic nutrition is essential during the peri-implantation development in rodents, but little is known about receptors involved in protein and lipid endocytosis derived from the endometrium and the uterine glands. Previous studies suggested that cubilin, a multiligand receptor for vitamin, iron, and protein uptake in the adult, might be important in this process, but the onset of its expression and function is not known. In this study, we analyzed the expression of cubilin in the pre- and early post-implantation rodent embryo and tested its potential function in protein and cholesterol uptake. Using morphological and Western blot analysis, we showed that cubilin first appeared at the eight-cell stage. It was expressed by the maternal-fetal interfaces, trophectoderm and visceral endoderm, but also by the future neuroepithelial cells and the developing neural tube. At all these sites, cubilin was localized at the apical pole of the cells exposed to the maternal environment or to the amniotic and neural tube cavities, and had a very similar distribution to megalin, a member of the LDLR gene family and a coreceptor for cubilin in adult tissues. To analyze cubilin function, we followed endocytosis of apolipoprotein A-I and HDL cholesterol, nutrients normally present in the uterine glands and essential for embryonic growth. We showed that internalization of both ligands was cubilin dependent during the early rodent gestation. In conclusion, the early cubilin expression and its function in protein and cholesterol uptake suggest an important role for cubilin in the development of the peri-implantation embryo.
authors.affiliation: Inserm, UMR 538, Faculté de Médecine Saint-Antoine, Paris, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Assémat
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Vinot
authors.forename: Françoise
authors.initials: F
authors.lastname: Gofflot
authors.forename: Patrick
authors.initials: P
authors.lastname: Linsel-Nitschke
authors.forename: Françoise
authors.initials: F
authors.lastname: Illien
authors.forename: François
authors.initials: F
authors.lastname: Châtelet
authors.forename: Pierre
authors.initials: P
authors.lastname: Verroust
authors.forename: Sophie
authors.initials: S
authors.lastname: Louvet-Vallée
authors.forename: Franz
authors.initials: F
authors.lastname: Rinninger
authors.forename: Renata
authors.initials: R
authors.lastname: Kozyraki
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001755:Blastocyst / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D010064:Embryo Implantation / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D004705:Endocytosis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D050356:Lipid Metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011506:Proteins; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor