Fetal Control of Calcium Transport across the Rat Placenta

Abstract

ABSTRACT. Control of maternofetal calcium transfer across the in situ perfused rat placenta at day 21 of gestation (term 23 d) was investigated in both intact fetuses and those parathyroidectomized by decapitation on day 19. Decapitation resulted in significant fetal hypocalcemia. Injection of fetuses subcutaneously through the uterine wall with 0.43 ~g bovine (b) PTH(1-84), 20 ng 1,25(OH),D3 or 10 FL of the appropriate diluent resulted 2 h later in a raised fetal blood ionized Ca concentration only with bPTH(1-84) in both normal and decapitated fetuses. Fetal decapitation caused a significant ( p < 0.001) fall in the clearance of 45Ca across the placenta (KmP5Ca), which was significantly ( p < 0.05) reversed after fetal bPTH(1-84) and 1,25 dihydroxy vitamin D3 (1,25(0H)2 D3) injection, but not back to normal levels. There was no effect of either hormone on K,P5Ca in placentas from intact fetuses, or on KmfSICr-EDTA (used as an extracellular marker) in either group. When 4 ng/mL r[Nle8321,Ty?4] PTH(1-34), 50 pg/mL 1,25(OH),D3 or the appropriate diluent was perfused through placentas the only response observed was a significant (p < 0.05) increase in KmP5Ca with 1,25(OH),D3 perfusion in placentas from decapitated fetuses, KmfSICr-EDTA being unchanged. Finally, perfusion with M forskolin (an activator of adenylate cyclase) stimulated KmP5Ca in placentas from both normal and decapitated fetuses. Although there was also some effect on KmfSICr-EDTA in the latter, there was none in the placentas from normal fetuses, and here the effect on KmP5Ca was dose dependent with an initial response at M. It is therefore suggested that fetal PTH and 1,25(0H),D3 may play a permissive role in the control of maternofetal calcium transfer and that other hormones which act via CAMP may be involved in the acute regulation of calcium transfer under normal conditions. (Pediatr Res 26: 109-115,1989) In the sheep there is evidence that prolactin may stimulate and calcitonin reduce net maternofetal calcium transfer (1, 2), and studies on fetally perfused sheep placenta suggests that PTHrP may stimulate calcium transfer (3). There have been few direct studies in other species (4) although fetal calcium homeostasis also appears to be autonomous in the rat. Thus PTH (5) and calcitonin (6) do not appear to cross the rat placenta and are presumably of fetal or placental (7, 8) origin, and the fetal parathyroids (9) and thyroid "C" cells (10) are active in utero.Fetal 1,25(OH)2D3 may be derived from the mother across the placenta (1 l), be produced by the placenta itself (l2), or by the fetal kidney (1 3), although the fall in plasma 1 ,25(OH)2D3 concentration after bilateral nephrectomy of the sheep fetus (14) suggests thatjn this species the fetal kidney is the major source.Stulc and Stulcova (1 5 ) have described a method for perfusing the fetal side of the rat placenta and demonstrated by this method active maternofetal calcium transport quantitatively similar to that found in vivo. We have also recently investigated the passive permeab...

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

“…Exogenous PTH 1-34 did modestly stimulate calcium transport in perfused placentas from rat fetuses that had been decapitated to crudely mimic parathyroidectomy (554), but it had no effect in perfused placentas from intact fetuses (554,611). Placentas from thyroparathyroidectomized rat fetuses were not studied.…”

“…Loss of parathyroids from any cause results in fetal hypocalcemia, as demonstrated in fetal lambs (thyroparathyroidectomy followed by replacement of thyroxine) (1, 2), rats (thyroparathyroidectomy or decapitation) (520,521,554), and mice (loss of parathyroids through genetic ablation of Hoxa3 or Gcm2, or loss of PTH alone in Pth null fetuses) (336,341,623).…”

“…Decapitation was done to crudely mimic parathyroidectomy, and (similar to the effects of thyroparathyroidectomy in fetal lambs) this resulted in a fall in placenta calcium transport (554). That deficit in placental calcium transport was increased slightly (but remained well below the normal value) after infusion of PTH (554); no PTHrP peptides were tested in the decapitation model. However, in perfused placentas from intact fetuses, PTH The creation of Pthrp null fetuses (297) enabled a different approach to measure placental calcium transport within intact fetuses using the methodology described in section IIF3.…”

“…The most rigorous technique is in situ placental perfusion, which has been used in lambs, goats, guinea pigs, and rats (97,433,554,654,723). The procedure begins by removing the fetus and connecting the placenta to a semi-closed circuit via the umbilical vessels (FIGURE 7).…”

“…51 Cr-EDTA is not actively transported but diffuses across these placentas, so its appearance within the umbilical vein is considered to reflect diffusion of isotope. The rate of active calcium transfer is calculated from formulas that incorporate the speed at which the 45 Ca concentration declines in the maternal circulation, and the rate at which the concentration of 45 Ca increases relative to 51 Cr-EDTA in the umbilical vein (554). Hormones, drugs, or antibodies can be infused into the umbilical artery (placental in-flow) to test their effects on fetal regulation of placental calcium transport, or into the maternal circulation to determine if there are maternal effects on the regulation of placental calcium transport (723).…”