Fetal-placental calcium metabolism in mice partly or fully deficient in parathyroid hormone

Simmonds, Charlene S. (2010) Fetal-placental calcium metabolism in mice partly or fully deficient in parathyroid hormone. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

It is well established that parathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult. The role, if any, of PTH in fetal-placental mineral homeostasis has been uncertain. Therefore, the purpose of the present doctoral research was to examine the role of PTH in fetal-placental calcium homeostasis. It was hypothesized that: PTH, despite its low circulating levels during fetal life, plays an important role in regulating not only fetal blood calcium and skeletal development, but also placental calcium transfer. To address this, two different genetic mouse models of PTH deficiency were utilized. The Pthtm1Dgo knockout (i.e. Pth null) mice served as a model of complete absence of PTH because they have enlarged parathyroids that are incapable of making PTH, while the Gcm2tm1Kry knockout ( i.e. Gcm2 null) mice served as a model of severe hypoparathyroidism because they lack parathyroids but have some PTH. Both nulls displayed a fetal hypoparathyroid phenotype, experiencing hypocalcemia, hypomagnesemia, hyperphosphatemia, low amniotic fluid mineral content, and reduced skeletal mineral content. When Pth null fetuses were treated in utero with PTH (1-84), placental calcium transfer increased, and placental gene expression was altered. It was also discovered that PTH is expressed in the placenta of wild-type and Gcm2 null fetuses. Thus, from the present study it is evident that PTH does indeed play an important role in fetal-placental mineral homeostasis. More specifically, PTH is important for fetal blood calcium, fetal skeletal development, is expressed locally in the placenta, regulates placental gene expression, and may directly regulate the transfer of calcium from mother to fetus.

Item Type: Thesis (Doctoral (PhD))
URI: http://research.library.mun.ca/id/eprint/9166
Item ID: 9166
Additional Information: Includes bibliographical references (leaves 133-157)
Department(s): Medicine, Faculty of
Date: 2010
Date Type: Submission
Library of Congress Subject Heading: Calcium--Metabolism; Maternal-fetal exchange; Parathyroid hormone
Medical Subject Heading: Calcium--metabolism; Maternal-Fetal Exchange; Parathyroid Hormone

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