Early Detection of Infants with Hypophosphatemic Vitamin D Resistant Rickets (HDRR).

Minamitani, Kanshi; Minagawa, Masahiro; Yasuda, Toshiyuki; Niimi, Hiroo

doi:10.1507/endocrj.43.339

Cited by 3 publications

(2 citation statements)

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“…In XLH patients, hypophosphatemia may not be detected at birth, resulting in difficulty with an early diagnosis. (34) In the current study, we found that the plasma levels of Pi in both Hyp fetuses and their WT littermates from hypophosphatemic Hyp mothers were comparable to those in WT fetuses from WT mothers (Fig. 2C, D), which is consistent with the observation in newborn babies of patients with XLH.…”

Section: Discussionsupporting

confidence: 90%

Elevated Fibroblast Growth Factor 23 Exerts Its Effects on Placenta and Regulates Vitamin D Metabolism in Pregnancy of Hyp Mice

Ohata

Yamazaki

Kawai

et al. 2014

Journal of Bone and Mineral Research

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Fibroblast growth factor 23 (FGF23) functions in an endocrine fashion and requires a-Klotho to exert its effects on the target organs. We have recently demonstrated that the human placenta also expresses a-Klotho, which led us to hypothesize that FGF23 may exert effects on the placenta. Immunohistochemical analysis demonstrated the expression of FGF receptor 1 (FGFR1) as well as that of a-Klotho in the feto-maternal interface of both mouse and human normal-term placentas, which suggested that these areas might be receptive to FGF23. Therefore, we next investigated whether FGF23 has some roles in the placenta using Hyp mice with high levels of circulating FGF23. Hyp and wild-type (WT) females were mated with WT males, and the mothers and their male fetuses were analyzed. FGF23 levels in Hyp mothers were elevated. FGF23 levels were about 20-fold higher in Hyp fetuses than in Hyp mothers, whereas WT fetuses from Hyp mothers exhibited low levels of FGF23, as did fetuses from WT mothers. We analyzed the placental gene expression and found that the expression of Cyp24a1 encoding 25OHD-24-hydroxylase, a target gene for FGF23 in the kidney, was increased in the placentas of fetuses from Hyp mothers compared with fetuses from WT mothers. In an organ culture of WT placentas, treatment with plasma from Hyp mothers markedly increased the expression of Cyp24a1, which was abolished by the simultaneous addition of anti-FGF23 neutralizing antibody. The direct injection of recombinant FGF23 into WT placentas induced the expression of Cyp24a1. The increase in the placental expression of Cyp24a1 in fetuses from Hyp mothers resulted in decreased plasma 25-hydroxyvitamin D levels. These results suggest that increased levels of circulating FGF23 in pathological conditions such as Hyp mice exerts direct effects on the placenta and affects fetal vitamin D metabolism via the regulation of Cyp24a1 expression.

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