Plasma Calcium Control in the Rat Fetus. I. Influence of Maternal Hormones

Abstract

The influence of PTH, calcitonin (CT), and thyroxine deficiencies during pregnancy on fetal plasma calcium and fetal growth has been investigated in thyroidectomized (TX) and thyroparathyroidectomized (TPTX) mother rats complemented or not with thyroxine. Maternal femurs analyses at 21.5 days of gestation in TX and TPTX rats showed a significant decrease in wet and dry weights, whereas percentage of ash and its relative content in calcium and phosphorus was unchanged. Thus, CT during pregnancy seemed to prevent a decrease in the organic part of bone. The fetus from TPTX mothers was characterized by a reduced body weight (––1.95 g) and a 12% drop in its percentage of ash. The length of the fetal femur was 16% decreased, the shaft being mainly affected. It the percentage of ash of the fetal femur was unchanged, its relative content in calcium and phosphorus was decreased. In fetuses from TX mothers, the body weight was slightly decreased (∼ 0.71 g) and the percentage of ash was 5% reduced. The small decrease in the fetal femur length reflected a change at the distal end. Thyroxine complementation in TX or TPTX mothers induced a normalization of the fetal percentage of ash in both cases; a trend towards an increased value was observed in the percentage of ash of fetal femurs. Fetuses from TX mothers exhibited normal plasma calcium values unaffected by maternal thyroxine complementation. The lowered plasma calcium level (∼ 2.5 mg/dl) occurring in fetuses from TPTX mothers was increased by 1 mg/dl after thyroxine complementation of the mother in spite of unaltered maternal plasma calcium levels.

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

“…Conversely, maternal hypocalcemia may impair the forward flow of calcium from mother to fetus, and force the fetal-placental unit to upregulate the mechanisms that maintain the fetal blood calcium and placental calcium transport. Consistent with this, maternal parathyroidectomy or calcitonin infusions in pregnant rats have been shown to cause a marked increase in fetal PTH, parathyroid gland hyperplasia, and bone resorption; the skeleton is undermineralized (104,206,541,542,625). …”

“…Similarly, when pregnant rats were hypocalcemic due to thyroparathyroidectomy or calcitonin infusions, the fetal bones showed increased resorption when subsequently cultured in vitro (541,542), the fetal parathyroids enlarged (206,625), and fetal femur length and mineral ash content were reduced (104). These findings in lambs and rats are compatible with a reduction in placental calcium transport that is sufficient to delay primary mineralization of bone or induce secondary hyperparathyroidism in the fetuses, while enabling the fetuses to maintain normal concentrations of minerals within the circulation.…”

“…In support of this, expression of a constitutively active PTH1R (Jansen receptor) within the endochondral skeleton increased the fetal serum calcium, including in double-mutants that also lacked Pthrp (330,596). Furthermore, the fetal skeleton can undergo increased osteoclast-mediated resorption in response to such factors as maternal hypocalcemia (104,377) or an inactivating mutation of CaSR (338), and present with an undermineralized skeleton or fractures at birth.…”

“…A normal serum calcium likely requires upregulation of placental calcium transfer to maintain it, and this is supported by the observation that an acute calcium infusion caused a marked rise in serum calcium of fetuses from thyroparathyroidectomized rats, but not in fetuses from thyroidectomized rats (106). The fetal skeleton may also be compromised by resorbing itself to maintain the normal high level of calcium in fetal blood, as seen by enlargement of the fetal parathyroids (206,625), increased resorption in fetal rat bones that requires intact fetal parathyroids for it to occur (542), and reduced femur length and mineral ash content (104). But even with overt hypocalcemia throughout pregnancy, the neonate can have a perfectly normal skeleton (217).…”

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

“…On the other hand, in a series of related studies from one laboratory, parathyroidectomized Wistar rats on a 0.9% calcium diet developed worsening hypocalcemia and hyperphosphatemia between 16.5 and 21.5 days of gestation, and up to 40% experienced tetany or sudden death either during late pregnancy or while giving birth (163,313,314,328). Serum calcitriol and intestinal expression of calbindin 9K -D levels in parathyroidectomized rats were ϳ50% of the values in intact rats at day 21.5 of pregnancy (313), but no earlier measurements were done.…”