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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...

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Background: Offspring of diabetic rats have reduced urinary calcium and magnesium excretion compared with offspring of controls; these differences persist up to16 weeks after birth, a time equivalent to young adulthood in humans. Objectives: To test the hypothesis that urinary calcium and magnesium excretion would be lower in children born to mothers with insulin dependent diabetes mellitus (ChMIDDM) than those born to nondiabetic mothers. Methods: Concentrations of calcium, magnesium, sodium, and creatinine were measured in first void spot urine samples collected from 45 (28 male; median age 9.6 years) ChMIDDM and 127 (58 male; median age 11.3 years) controls. Analysis of covariance was used to test for differences in urinary calcium to creatinine ratios (UCa/Cr), magnesium to creatinine ratios (UMg/Cr), and log sodium to creatinine ratios (logUNa/Cr) between controls and ChMIDDM after allowing for the effects of sex and age. Results: UCa/Cr (difference 20.10, 95% confidence interval (CI) 20.19 to 20.01; p = 0.03) and UMg/ Cr (difference 20.15, 95% CI 20.22 to 20.08; p,0.0001) were lower in ChMIDDM than controls. However, logUNa/Cr did not differ between ChMIDDM and controls (difference 20.14, 95% CI 20.33 to 0.05; p = 0.1). The daily estimated intake of magnesium, sodium, and protein were significantly higher and that of calcium non-significantly higher in ChMIDDM than controls. In ChMIDDM, UCa/Cr and UMg/ Cr were not related to diabetic control of mothers. Conclusions: Results of this study provide the first evidence that in humans, as in rats, there is modification of renal Ca and Mg handling in ChMIDDM, which persists well into childhood.

Two human parathyroid hormone-related protein (hPTHrP) fragments were tested for effects on maternofetal transfer of 45Ca and Mg across the in-situ perfused rat placenta at 21 days of gestation (term = 23 days). The fetal placental circulation was perfused with a Mg-free Krebs-Ringer solution and the unidirectional maternofetal clearance (Kmf) of 45Ca and Mg compared with that of 51Cr-EDTA, the latter being employed as a paracellular diffusional marker. Placental perfusion with hPTHrP(1-34) (100 ng/ml) or hPTHrP(75-86)amide (50 ng/ml) did not significantly alter the Kmf of 45Ca or that of Mg. In separate rats, however, hPTHrP(1-34) but not hPTHrP(75-86)amide stimulated marked placental cyclic AMP (cAMP) release, the peak response of 63 +/- 7 pmol/min occurring 10 min after the beginning of the peptide perfusion. A lower dose of hPTHrP(1-34) (4 ng/ml) produced a similar peak release of cAMP, as did [Nle8,21, Tyr34]-rPTH(1-34)amide (4 ng/ml) and the adenylate cyclase agonist forskolin (17 mumol/l). Forskolin also rapidly increased the Kmf of 45Ca but not that of Mg or 51Cr-EDTA. The present study indicates that hPTHrP does not acutely affect maternofetal transfer of Ca or Mg across the perfused rat placenta. The data also question the role played by cAMP in the stimulatory actions of forskolin on placental Ca transport.

ABSTRACT. Mechanisms of maternofetal Mg transfer gradient does not reflect greater protein binding in fetal plasma, have been investigated across the in situ perfused rat ultrafiltrable Mg concentrations also being higher in fetal complacenta at 21 d gestation (term = 23 d). The fetal placental pared with maternal plasma (1). These observations indicate that circulation was perfused with Mg-free Krebs-Ringer solu-placental transfer of Mg from mother to fetus must occur against tion and clearance of Mg from maternal plasma across the a chemical gradient. Using '*Mg, Care et al. (4) determined placenta [unidirectional maternofetal clearance (K,3 Mg] maternofetal and fetomaternal Mg fluxes of 0.042 and 0.012 compared with that for 4sCa and "Cr-EDTA, the latter mg. h-I. kg-' fetus, respectively, in sheep at 13 d preterm. These being used as a diffusional marker. Because diffusion coef-fluxes suggest the presence of an active mechanism for the ficients determined for these solutes were similar (6.8-7.6 maternofetal transfer of Mg. x cm2.sec-I), greater Kmf values determined for Mg In our study, maternal and fetal plasma Mg concentrations and 45Ca (mean f SD: 26.7 f 9.2 and 93.1 f 29.8 pL. (total and ultrafiltrable) were measured in the near term rat and min-' .g-' placenta, respectively) compared to "Cr-EDTA maternofetal Mg transfer was investigated using the in situ (um-(3.2 f 0.9 pL . min-' . g-I) suggest that maternofetal trans-bilically) perfused rat placenta preparation (7). K,f of 24Mg was fer of these cations occurs by mechanisms in addition to compared with that of "Cr-EDTA, used as a diffusional marker diffusion. Kmf Mg was also greater than Kmf "Cr-EDTA (7), and also with that of 45Ca, a divalent cation with which Mg when measured across the dually perfused rat placenta, in may share transcellular transport systems (8). Previous studies which the maternal uterine artery was additionally perfused (9) suggest that Ca is actively transferred across the in situ with Mg-containing (0.5 mmol. L-') Krebs-Ringer solu-perfused rat placenta. The effects of adding KCN to the perfusion tion. Decreasing the Mg concentration in the maternal fluid or decreasing perfusate temperature were therefore examperfusate by 90% reduced Mg appearance in the fetal ined for effects on possible active placental transfer of Mg as well perfusate by 87% within 8 min; this suggests that Kmf Mg as of 45Ca. Experiments were also performed using a dually across the in situ perfused placenta largely reflects Mg perfused rat placenta in which the maternal uterine artery was transfer from maternal plasma and not simply elution of a additionally perfused with Krebs Ringer solution with or without placental Mg pool. Addition of KCN (1 mrno1.L-I) to the Mg (10). These were performed to confirm that Mg transfer (as fetal perfusate or lowering perfusate temperature from 37 measured using the in situ perfused placenta) reflects maternoto 26°C significantly reduced Kmf Mg and Kmf 45Ca across fetal transfer and not simply elution of a placental Mg poo...

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