Intrauterine growth restriction (IUGR) is observed in conditions with limitations in uterine space (e.g., uterine anomalies and multifetal gestations). IUGR is associated with reduced fetal weight, organ growth, and a spectrum of adult-onset diseases. To examine the interaction of uterine anomalies and multifetal gestations, we developed a surgical uterine space restriction model with a unilateral uterine horn ligation before breeding (unilateral surgery). Placentas and fetuses were studied on Gestational Day (GD) 120 and GD 130 (term = 147 days). Unilateral surgery decreased placentome numbers in singleton and twin pregnancies (25% and 50%, respectively) but not unilateral triplets. Unilateral surgery decreased total placentome weight in twin pregnancies (decreased 24%). Fetuses categorized as uterine space restricted (unilateral twin and both groups of triplets) had 51% fewer placentomes per fetus and a 31% reduction in placentomal weight per fetus compared to the nonrestricted group (control singleton, unilateral singleton, and control twin). By GD 130, uterine space-restricted fetuses exhibited decreased weight, smaller crown-rump, abdominal girth, and thoracic girth as well as decreased fetal heart, kidney, liver, spleen, and thymus weights. Lung and brain weights were unaffected, demonstrating asymmetric IUGR. At GD 130, placental efficiency (fetal weight per total placentomal weight) was elevated in uterine space-restricted fetuses. However, fetal arterial creatinine, blood urea nitrogen, and cholesterol were elevated, suggesting insufficient placental clearance. Maternal-to-fetal glucose and triglycerides ratios were elevated in the uterine space-restricted pregnancies, suggesting placental nutrient transport insufficiency. This model allows for examination of interactive effects of uterine space restriction-induced IUGR on placental adaptation and fetal organ growth.

BackgroundFetal growth restriction is reported to be associated with impaired placental iron transport. Transferrin receptor (TfR) is a major placental iron transporter in humans, but is unstudied in sheep. TfR is regulated by both iron and nitric oxide (NO), the molecule produced by endothelial NOS (eNOS). We hypothesized that limited placental development downregulates both placental TfR and eNOS expression, thereby lowering fetal tissue iron.MethodsAn ovine surgical uterine space restriction (USR) model, combined with multifetal gestation, tested the extremes of uterine and placental adaptation. Blood, tissues, and placentomes from non-space restricted (NSR) singletons were compared to USR fetuses at 120 or 130 days of gestation (GD).ResultsWhen expressed proportionate to fetal weight, liver iron content did not differ while renal iron was higher in USR vs. NSR fetuses. Renal TfR protein expression did not differ, but placental TfR expression was lower in USR fetuses at GD130. Placental levels of TfR correlated to eNOS. TfR was localized throughout the placentome, including the hemophagous zone, implicating a role for TfR in ovine placental iron transport.ConclusionIn conclusion, fetal iron was regulated in an organ-specific fashion. In USR fetuses, NO-mediated placental adaptations may prevent the normal upregulation of placental TfR at GD130.

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A study on the mechanism by which sevelamer hydrochloride (Sev), a polymeric phosphate binder, lowers plasma phosphorus in end‐stage renal failure patients was conducted using a day‐old chick model. Three pens of 5 broiler‐type male chicks/treatment were fed a diet marginally deficient in phosphorus (diet 1, P deficient), diet 1 plus adequate inorganic phosphorus (diet 2), diet 1 plus 20ug/Kg 1 alpha‐OH D3 (diet 3), diet 2 plus 2 g/Kg diet Sev, or diet 3 plus 2g/Kg diet Sev. After three weeks, all chicks were weighed, bled (to determine plasma phosphorus), and the right tibiotarsus was collected for determination of dry fat‐free bone ash. Addition of phosphorus or 1 alpha‐OH D3 to the P deficient diet (diet 1) increased weight, bone ash, and plasma phosphorus as compared to chicks fed a phosphorus deficient diet (p<0.001). Addition of Sev was ineffective at reducing body weight, plasma phosphorus or bone ash when phosphorus was made adequate using inorganic phosphorous, but did decrease these variables when added to the diet supplemented with 1 alpha‐OH D3 (p<0.001). These data showed that Sev, at the dose used, was not able to counteract improved phosphorus status associated with inorganic phosphorus supplementation but was effective in preventing improved phosphorus status resulting from the addition of 1 alpha‐OH D3. This work was supported by the Wisconsin Alumni Research Foundation.