PMID- 23202722 OWN - NLM STAT- MEDLINE DCOM- 20130812 LR - 20211021 IS - 1530-0447 (Electronic) IS - 0031-3998 (Print) IS - 0031-3998 (Linking) VI - 73 IP - 3 DP - 2013 Mar TI - Ovine uterine space restriction alters placental transferrin receptor and fetal iron status during late pregnancy. PG - 277-85 LID - 10.1038/pr.2012.180 [doi] AB - BACKGROUND: Fetal growth restriction is reported to be associated with impaired placental iron transport. Transferrin receptor (TfR) is a major placental iron transporter in humans but has not been studied in sheep. TfR is regulated by both iron and nitric oxide (NO), the molecule produced by endothelial nitric oxide synthase (eNOS). We hypothesized that limited placental development downregulates both placental TfR and eNOS expression, thereby lowering fetal tissue iron. METHODS: An 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 with USR fetuses at gestational day (GD) 120 or 130. RESULTS: When expressed proportionate to fetal weight, liver iron content did not differ, whereas 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. CONCLUSION: Fetal iron was regulated in an organ-specific manner. In USR fetuses, NO-mediated placental adaptations may prevent the normal upregulation of placental TfR at GD130. FAU - Sun, Mary Y AU - Sun MY AD - Department of Pediatrics, Perinatal Research Laboratory, University of Wisconsin, Madison, Wisconsin, USA. FAU - Habeck, Jason M AU - Habeck JM FAU - Meyer, Katie M AU - Meyer KM FAU - Koch, Jill M AU - Koch JM FAU - Ramadoss, Jayanth AU - Ramadoss J FAU - Blohowiak, Sharon E AU - Blohowiak SE FAU - Magness, Ronald R AU - Magness RR FAU - Kling, Pamela J AU - Kling PJ LA - eng GR - HL087144/HL/NHLBI NIH HHS/United States GR - HL49210/HL/NHLBI NIH HHS/United States GR - HD38843/HD/NICHD NIH HHS/United States GR - R01 HL087144/HL/NHLBI NIH HHS/United States GR - P01 HD038843/HD/NICHD NIH HHS/United States GR - R01 HL049210/HL/NHLBI NIH HHS/United States GR - R01 HL117341/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20121130 PL - United States TA - Pediatr Res JT - Pediatric research JID - 0100714 RN - 0 (Receptors, Transferrin) RN - E1UOL152H7 (Iron) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - Analysis of Variance MH - Animals MH - Blotting, Western MH - Body Weights and Measures MH - Female MH - Fetus MH - Gene Expression Regulation, Developmental/*physiology MH - Immunohistochemistry MH - Iron/*metabolism MH - Kidney/anatomy & histology/metabolism MH - Nitric Oxide Synthase Type III/*metabolism MH - Organ Size/physiology MH - Placenta/*metabolism MH - Placentation MH - Pregnancy MH - Receptors, Transferrin/*metabolism MH - Sheep MH - Uterus/anatomy & histology/*physiology PMC - PMC3678369 MID - NIHMS447508 EDAT- 2012/12/04 06:00 MHDA- 2013/08/13 06:00 PMCR- 2013/09/01 CRDT- 2012/12/04 06:00 PHST- 2012/12/04 06:00 [entrez] PHST- 2012/12/04 06:00 [pubmed] PHST- 2013/08/13 06:00 [medline] PHST- 2013/09/01 00:00 [pmc-release] AID - pr2012180 [pii] AID - 10.1038/pr.2012.180 [doi] PST - ppublish SO - Pediatr Res. 2013 Mar;73(3):277-85. doi: 10.1038/pr.2012.180. Epub 2012 Nov 30.