title: Neither absence nor excess of FGF23 disturbs murine fetal-placental phosphorus homeostasis or prenatal skeletal development and mineralization.
abstract: Fibroblast growth factor-23 (FGF23) controls serum phosphorus largely through actions on the kidneys to excrete phosphorus and reduce calcitriol. Although these actions are well established in adults and children, the role that FGF23 plays in regulating fetal phosphorus metabolism has not been previously studied. We used several mouse models to study the effect of endogenous deficiency or excess of FGF23 on fetal phosphorus metabolism. We found that intact FGF23 does not cross the placenta from mother to fetus, but wild-type fetuses normally have intact FGF23 levels that approximately equal the maternal level. Deletion of Fgf23 or 7.8-fold higher serum FGF23 levels did not disturb any parameter of fetal mineral homeostasis, including serum and amniotic fluid phosphorus, skeletal morphology, skeletal mineral content, and placental phosphorus transport. Placentas and fetal kidneys abundantly express FGF23 target genes. Cyp24a1 was significantly reduced in Fgf23 null kidneys and was significantly increased in Phex null placentas and fetal kidneys. Phex null kidneys also showed reduced expression of Klotho. However, these changes in gene expression did not disturb any physiological parameter related to phosphorus. A 50% reduction in FGF23 also failed to affect renal phosphorus excretion into amniotic fluid when either PTH or the vitamin D receptor were absent. In conclusion, FGF23 is not an important regulator of fetal phosphorous metabolism. The active delivery of phosphorus across the placenta does not require FGF23, and that process overrides any effects that absence or excess of FGF23 might otherwise have on phosphate handling by the fetal kidneys.
authors.affiliation: Faculty of Medicine-Endocrinology (Y.M., M.S., S.C.-H., B.J.K., C.S.K.), Memorial University of Newfoundland, St John's, Newfoundland and Labrador, Canada A1B 3V6; McGill University and Jewish General Hospital, Montréal (A.C.K.), Québec, Canada H3T 1E2; and Department of Oral Medicine, Infection and Immunity (B.L.), Harvard School of Dental Medicine, Boston, Massachusetts 02115-5819.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.forename: Manoharee
authors.initials: M
authors.lastname: Samaraweera
authors.forename: Sandra
authors.initials: S
authors.lastname: Cooke-Hubley
authors.forename: Beth J
authors.initials: BJ
authors.lastname: Kirby
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Karaplis
authors.forename: Beate
authors.initials: B
authors.lastname: Lanske
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Kovacs
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic; D005260:Female; D005312:Fetal Blood; D047109:Fetal Development; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010012:Osteogenesis; D010758:Phosphorus / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: C000717428:Fgf23 protein, mouse; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23