Abstract

Inorganic phosphate (Pi) is an essential nutrient that fulfills critical roles in human health. It enables skeletal ossification, supports cellular structure and organelle function, and serves key biochemical roles in energetics and molecular signaling. Pi homeostasis is modulated through diet, intestinal uptake, renal reabsorption, and mobilization of stores in bone and extracellular compartments. Disrupted Pi homeostasis is associated with phosphate wasting, mineral and bone disorders, and vascular calcification. Mechanisms of Pi homeostasis in pregnancy remain incompletely understood. The study presented herein examined biological fluid Pi characteristics over the course of gestation. Correlations with gestation age, pregnancy number, preterm birth, preeclampsia, diabetes mellitus, and placental calcification were evaluated during the last trimester. The results support that maternal urinary Pi levels increased during the third trimester of pregnancy. Reduced levels were observed with previous pregnancy. Amniotic fluid Pi levels decreased with gestation while low second trimester levels associated with preterm birth. No significant difference in urinary Pi levels was observed between preeclampsia and controls (8.50 ± 2.74 vs. 11.52 ± 2.90 mmol/L). Moreover, increased maternal urinary Pi was associated with preexisting diabetes mellitus in preeclampsia. Potential confounding factors in this study are maternal age at delivery and body mass index (BMI)—information which we do not have access to for this cohort. In conclusion, Pi levels provide clinical information regarding the pathogenesis of pregnancy-related complications, supporting that phosphate should be examined more closely and in larger populations.

Highlights

  • Phosphorus is an essential micronutrient that serves as key biochemical roles in cellular structure, organelle function, energetics and molecular signaling, and skeletal ossification

  • Disrupted Pi homeostasis is associated with Pi wasting, refeeding syndrome, chronic kidney disease (CKD) mineral and bone mineralization disorders (BMD), and medial vascular calcification

  • Pi homeostasis is regulated through multi-system endocrine signaling in conjunction with calcium via systemic activity of phosphatonins including parathyroid hormone (PTH), vitamin D (VD), and fibroblast growth factor 23 (FGF23)

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Summary

Introduction

Phosphorus is an essential micronutrient that serves as key biochemical roles in cellular structure, organelle function, energetics and molecular signaling, and skeletal ossification. In early preeclampsia (PE), placental expression of the sodium-dependent phosphate transporters Slc20a1 and Slc20a2 is highly reduced; yet in late PE, Slc20a2 is significantly increased [3]. The cause for these alterations remains unknown. High levels of dietary Pi consumption and high circulating levels of Pi induce ectopic medial vascular calcification, the deposition of calcium-phosphate mineral in the smooth muscle cell layer of blood vessels. Vascular calcification requires phosphate for the chemical foundation of the calcium-phosphate mineral, in the form of hydroxyapatite, and high Pi levels induce pathological expression of osteochondrogenic proteins by smooth muscle cells [25,26,27]. The aim of this research was to examine biological fluid (maternal urine, amniotic fluid) Pi characteristics over the course of gestation and to evaluate correlation with gestational age at delivery, pregnancy number, preterm birth, preeclampsia, diabetes mellitus, and placental calcification

Nonhuman Subjects Research
GAPPS Cohort Samples
OHSU Amniotic Fluid Samples
Pi Quantification
Methods for Von Kossa Staining and Imaging of Placenta Tissue
Statistical Analysis of Experimental Data
Clinical Characteristics
Findings
16. ACOG Practice Bulletin No 202
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