title: FcRn Expression on Placenta and Fetal Jejunum during Early, Mid-, and Late Gestation in Minipigs.
abstract: Developmental toxicity testing of therapeutic antibodies is most often conducted in nonhuman primates owing to lack of cross-reactivity in other species. Minipigs may show cross-reactivity for some humanized antibodies but have not been used for developmental toxicity testing due to an assumed lack of embryo-fetal exposure. Unlike in humans, maternal IgGs do not cross the porcine placenta to reach the fetus. Some humanized IgGs, however, have a higher affinity for the neonatal Fc receptor (FcRn) and are more likely than endogenous antibodies to cross the placenta of animals. The major site of prenatal IgG transfer is the placenta, though FcRn in fetal intestine could also uptake maternal IgGs from swallowed amniotic fluid. Using immunohistochemistry andin situhybridization in this experiment, FcRn was found in minipig placenta and fetal intestine during early, mid-, and late gestation. To date, however, fetal exposure to maternally administered IgGs has never been demonstrated in the minipig.
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland bjoern.jacobsen@roche.com.
authors.forename: Björn
authors.initials: B
authors.lastname: Jacobsen
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Hill
authors.affiliation: WIL Research Europe-Lyon, Saint-Germain-Nuelles, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Reynaud
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Adam
authors.initials: A
authors.lastname: Hey
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Barrow
mesh_terms: D000818:Animals; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism*; D007583:Jejunum / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010920:Placenta / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011961:Receptors, Fc / Q000032:analysis / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; C100688:Fc receptor, neonatal
keywords: FcRn; fetal intestine; minipig; placenta