ECTS Abstracts (2015) 1 P81

Klotho null foetuses reveal that FGF23 does not regulate foetal-placental phosphorus homeostasis or prenatal bone formation and mineralisation

Yue Ma, Beth J Kirby & Christopher S Kovacs

Memorial University of Newfoundland, St. John’s, NL, Canada.

Fibroblast growth factor-23 (FGF23) regulates serum phosphorus by acting on kidneys to excrete phosphorus and reduce calcitriol. Absence of FGF23 causes severely disturbed phosphorus and bone metabolism. In contrast, Fgf23 null foetuses at embryonic day (ED) 17.5 and 18.5 had normal phosphorus and skeletal parameters. In order to rule out that another phosphate-regulating FGF compensates for loss of FGF23 in utero, we studied the effect of loss of the FGF23 co-receptor Klotho, which causes a phenotype similar to loss of FGF23 in postnatal mice and humans. We mated Klotho+/- mice and studied their WT, Klotho+/-, and Klotho null foetuses. On ED 17.5, amniotic fluid (largely urine) was collected and placental 32P transport at 5 min was measured. Whole bodies at ED 18.5 were reduced to ash and the mineral content was assayed. At ED 18.5, serum and tibial sections were obtained. qPCR was done on ED 18.5 placentas and kidneys. Intact FGF23 was measured by EIA (Kainos). There was no alteration is foetal serum phosphorus (3.04±0.05 mM in WT, 3.01±0.06 mM in null), amniotic fluid phosphorus (1.75±0.15 mM in WT, 1.83±0.13 mM in null), placental 32P transport (90±9% in WT, 89±11% in null), serum FGF23 (107±14 pg/mL in WT, 138±14 pg/mL in null), or serum calcium and amniotic fluid calcium. Klotho nulls had normal tibial lengths, morphology, and mineralisation; and whole body skeletal ash weight and content of calcium, phosphorus, and magnesium. qPCR of placentas and kidneys confirmed absence of Klotho in the nulls but normal expression of Cyp27b1, Cyp24a1, Fgf23, Fgfr1-4, and NaPi2a,b&c. In conclusion, since loss of FGF23 or Klotho have no effect, FGF23 is clearly not a regulator of foetal-placental phosphorous and bone metabolism. Active transplacental delivery of phosphorus does not require FGF23 or Klotho, and supersedes FGF23’s potential effects on phosphate handling by foetal kidneys.

Disclosure: The authors declared no competing interests. This work was supported by operating grants from the Canadian Institutes of Health Research (#126469) and the Research & Development Corporation of Newfoundland and Labrador (5404.1145.102).

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