Plenary Poster 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019
Loss of FGF23 does not alter fetal mineral homeostasis except during maternal phosphate loading (#95)
Fgf23 and Klotho null fetuses display normal phosphate and bone metabolism; FGF23 appears to play no role until after birth. However, in such studies all fetuses received a normal phosphate load because maternal serum phosphorus (serumP) was normal.
We studied whether maternal dietary phosphate loading invokes a fetal FGF23 or PTH response.
Study1: 30 C57BL/6 females received low (0.3%), normal (0.7%) or high phosphate (1.65%) diets. One day before expected birth, maternal and fetal samples were collected.
Study2: 20 Fgf23+/-females on normal or high phosphate diets were mated to Fgf23+/-males and identical sample collections were done.
ANOVA and Tukey’s were used for multiple comparisons.
Study1: increasing phosphate intake resulted in higher maternal serumP (1.61±0.22 vs. 2.64±0.10 vs. 3.11±0.14 mM; p<0.05) and FGF23 (62.7±29.5 vs. 676±66.3 vs. 818±18.4 pg/mL; p<0.05) during pregnancy, while PTH stayed suppressed. Fetal serumP remained independent of maternal serumP (3.53±0.13 vs. 3.95±0.19 vs. 3.73±0.27 mM; p=NS). Fetal FGF23 and PTH remained low. There were no differences in fetal ash weight, phosphate, or calcium content; and no changes in placental expression of phosphate-related genes by qPCR.
Study2: high phosphate diet increased maternal FGF23 (889±66 vs. 525±57 pg/mL, p<0.001) while PTH stayed suppressed. Fgf23 null fetuses from mothers on the high phosphate diet had very high serumP compared to Fgf23 nulls from the normal diet (4.22±0.06 vs. 2.50±0.14 mM, p<0.001); PTH remained low. SerumP, FGF23, and PTH of WT fetuses were unaffected by the high phosphate diet. There were no differences across genotypes or diets in ash weight, phosphate, or calcium content. Fgf23 null placentas from the high phosphate diet had no changes in target gene expression.
In conclusion, maternal and fetal FGF23 (but not PTH) defend against fetal hyperphosphatemia, but the importance of fetal FGF23 becomes evident only by its absence during maternal phosphate loading.
