Abstract

Knowledge of gene expression profiles reflecting functional features and specific responsiveness of parathyroid glands (PTGs) contributes to understanding mineral homeostasis and parathyroid function in healthy and diseased conditions. The study aims to reveal effector molecules driving the maintenance of phosphorus (P) homeostasis and parathyroid hormone (PTH) responsiveness to variable P supply throughout fetal and postnatal life. In this study, a long-term dietary intervention was performed by keeping pig offspring on distinct mineral P levels throughout fetal and postnatal life. Respective adaptation processes of P homeostasis were assessed in mRNA profiles of PTGs and serum minerals. RNA sequencing data and resulting molecular pathways of PTGs showed that the PTH abundance is very strictly controlled via e.g., PIN1, CaSR, MAfB, PLC and PKA signaling to regulate PTH expression, stability, and secretion. Additionally, the observed dietary effects on collagen expression indicate shifts in the ratio between connective tissue and parenchyma, thereby affecting cell-cell contacts as another line of PTH regulation. Taken together, the mRNA profiles of porcine PTGs reflect physiological responses in-vivo following variable dietary P supplies during fetal and postnatal life. The results serve to evaluate a long-term nutrition strategy with implications for improving the mineral balance in individuals with pathological disorders.

Highlights

  • The maintenance of the mineral homeostasis is essential for ensuring the physical integrity of all vertebrates

  • Serum has been collected at day of life and parathyroid glands (PTGs) have been sampled at day of life

  • Offspring of low P fed mothers tend to be superior to offspring of other sow groups in all traits when receiving a low P diet themselves, implying subtle conditioning to cope with their own limited P supply (Tables 1 and 2)

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Summary

Introduction

The maintenance of the mineral homeostasis is essential for ensuring the physical integrity of all vertebrates. Endogenous adaptive mechanisms targeting the maintenance of mineral homeostasis could compensate a low dietary P supply to certain extents [2,3,4]. Early life periods are considered vulnerable to dietary challenges [5], which has been summarized in the concept of ‘Nutritional Programming’ [6,7]. It basically claims that a structure or tissue become permanently altered due to physiological responses to external stimuli such as a dietary pattern in early life [8]. Nutritional Programming might offer possible explanations for the onset of metabolic disorders [9], and provide opportunities to promote endogenous mechanisms towards an efficient nutrient utilization and Biomedicines 2021, 9, 454.

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