Placental-Specific Igf2 Knockout Mice Exhibit Hypocalcemia and Adaptive Changes in Placental Calcium Transport

• Published in: Proceedings of the National Academy of Sciences - PNAS 2010-02, Vol.107 (8), p.3894-3899
• Main Authors: Dilworth, M. R., Kusinski, L. C., Cowley, E., Ward, B. S., Husain, S. M., Constância, M., Sibley, C. P., Glazier, J. D., Roberts, R. Michael
• Format: Article
• Language: English
• Subjects: Amino acid transport systems; Animals; Biological Sciences; Blood plasma; Calcium; Calcium - metabolism; Cell membranes; Disease Models, Animal; Embryos; Female; Fetal Growth Retardation - genetics; Fetal Growth Retardation - metabolism; Fetus; Fetus - metabolism; Fetuses; Hypocalcemia - genetics; Hypocalcemia - metabolism; Insulin-Like Growth Factor II - genetics; Ion Transport; Male; Maternal-Fetal Exchange; Mice; Mice, Inbred C57BL; Mice, Knockout; Placenta; Placenta - metabolism; Pregnancy; Prenatal development; Proteins; Receptors; Rodents; Trophoblasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0911710107

Evidence is emerging that the ability of the placenta to supply nutrients to the developing fetus adapts according to fetal demand. To examine this adaptation further, we tested the hypothesis that placental maternofetal transport of calcium adapts according to fetal calcium requirements. We used a mouse model of fetal growth restriction, the placental-specific Igf2 knockout (PO) mouse, shown previously to transiently adapt placental System-A amino acid transporter activity relative to fetal growth. Fetal and placental weights in P0 mice were reduced when compared with WT at both embryonic day 17 (E17) and E19. Ionized calcium concentration [Ca²⁺] was significantly lower in PO fetal blood compared with both WT and maternal blood at E17 and E19, reflecting a reversal of the fetomaternal [Ca²⁺] gradient. Fetal calcium content was reduced in P0 mice at E17 but not at E19. Unidirectional maternofetal calcium clearance $(^{Ca} K_{mf} )$ was not different between WT and P0 at E17 but increased in P0 at E19. Expression of the intracellular calcium-binding protein $calbindin - D_{9K} $ , previously shown to be rate-limiting for calcium transport, was increased in P0 relative to WT placentas between E17 and E19. These data show an increased placental transport of calcium from E17 to E19 in P0 compared to WT. We suggest that this is an adaptation in response to the reduced fetal calcium accumulation earlier in gestation and speculate that the ability of the placenta to adapt its supply capacity according to fetal demand may stretch across other essential nutrients.