RESUMEN
We used the calcitonin/calcitonin gene-related peptide (CGRP)-alpha gene knockout model (Ct/Cgrp null) to determine whether calcitonin and CGRPalpha are required for normal fetal mineral homeostasis and placental calcium transfer. Heterozygous (Ct/Cgrp(+/-)) and Ct/Cgrp null females were mated to Ct/Cgrp(+/-) males. One or two days before term, blood was collected from mothers and fetuses and analyzed for ionized Ca, Mg, P, parathyroid hormone (PTH), and calcitonin. Amniotic fluid was collected for Ca, Mg, and P. To quantify skeletal mineral content, fetuses were reduced to ash, dissolved in nitric acid, and analyzed by atomic absorption spectroscopy for total Ca and Mg. Placental transfer of (45)Ca at 5 min was assessed. Ct/Cgrp null mothers had significantly fewer viable fetuses in utero compared with Ct/Cgrp(+/-) and wild-type mothers. Fetal serum Ca, P, and PTH did not differ by genotype, but serum Mg was significantly reduced in null fetuses. Placental transfer of (45)Ca at 5 min was normal. The calcium content of the fetal skeleton was normal; however, total Mg content was reduced in Ct/Cgrp null skeletons obtained from Ct/Cgrp null mothers. In summary, maternal absence of calcitonin and CGRPalpha reduced the number of viable fetuses. Fetal absence of calcitonin and CGRPalpha selectively reduced serum and skeletal magnesium content but did not alter ionized calcium, placental calcium transfer, and skeletal calcium content. These findings indicate that calcitonin and CGRPalpha are not needed for normal fetal calcium metabolism but may regulate aspects of fetal Mg metabolism.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/fisiología , Calcitonina/fisiología , Calcio/metabolismo , Feto/metabolismo , Magnesio/metabolismo , Líquido Amniótico/metabolismo , Animales , Calcitonina/deficiencia , Calcitonina/genética , Péptido Relacionado con Gen de Calcitonina/deficiencia , Péptido Relacionado con Gen de Calcitonina/genética , Calcio/sangre , Desarrollo Embrionario y Fetal/fisiología , Femenino , Sangre Fetal/metabolismo , Regulación del Desarrollo de la Expresión Génica , Placa de Crecimiento/metabolismo , Homeostasis/genética , Homeostasis/fisiología , Tamaño de la Camada/genética , Tamaño de la Camada/fisiología , Magnesio/sangre , Masculino , Intercambio Materno-Fetal/fisiología , Ratones , Ratones Noqueados , Placenta/metabolismo , Placentación , Embarazo , Preñez/sangre , ARN Mensajero/análisisRESUMEN
The expression of calcitropic genes and proteins was localized within murine placenta during late gestation (the time frame of active calcium transfer) with an analysis of several gene-deletion mouse models by immunohistochemistry and in situ hybridization. Parathyroid hormone-related protein (PTHrP), the PTH/PTHrP receptor, calcium receptor, calbindin-D(9k), Ca(2+)-ATPase, and vitamin D receptor were all highly expressed in a localized structure of the murine placenta, the intraplacental yolk sac, compared with trophoblasts. In the PTHrP gene-deleted or Pthrp-null placenta in which placental calcium transfer is decreased, calbindin-D(9k) expression was downregulated in the intraplacental yolk sac but not in the trophoblasts. These observations indicated that the intraplacental yolk sac contains calcium transfer and calcium-sensing capability and that it is a probable route of maternal-fetal calcium exchange in the mouse.