Bone Abstracts

Fibroblast growth factor-23 (FGF23) controls serum phosphorus by acting on the kidneys to excrete phosphorus and reduce calcitriol. These actions are well established in adults and children, but whether FGF23 regulates fetal phosphorus metabolism is unknown. We used X-linked Hyp or Phex null male fetuses to study the effect of excess FGF23 on fetal phosphorus metabolism. Phex^+/− females and WT males were mated to generate WT, Phex^+/− female, and Phex null male fetuses. Reverse matings of WT female to Phex null males were also done. All studies were approved by the local ethics committee.

Phex^+/− mothers had low serum phosphorus compared to WT mothers, but maternal hypophosphatemia did not affect fetal serum phosphorus levels. Phex^+/− female and Phex null male fetuses had 7.8-fold higher serum FGF23 levels than WT littermates. Increased FGF23 did not affect fetal serum calcium and phosphorus, urine (amniotic fluid) calcium and phosphorus, parathyroid hormone, skeletal morphology or limb lengths, tibial growth plate morphology, skeletal ash weight, and skeletal calcium and phosphorus. Serum calcitriol was reduced in Phex null male fetuses (WT 52.0±5.8, Phex null 34.7±2.6 pmol/l, P<0.013). We administered ³²P/⁵¹Cr-EDTA by intracardiac injection to pregnant mothers and found no difference among genotypes in placental transport of ³²P after 5 min. WT placentas and fetal kidneys abundantly expressed FGF23 target genes, including Cyp27b1, Cyp24a1, Klotho, NaPi2a, NaPi2b, NaPi2c, and FGF receptors 1–4. Of these, Cyp24a1 was significantly increased in Phex null placentas and fetal kidneys, while Klotho was significantly reduced in Phex null kidneys. However, these changes in gene expression did not disturb fetal phosphorus parameters.

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 overrides any effect that excess FGF23 might otherwise have on phosphate handling by fetal kidneys.