PMID- 37487938 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20231003 IS - 1096-0333 (Electronic) IS - 0041-008X (Print) IS - 0041-008X (Linking) VI - 475 DP - 2023 Sep 15 TI - Cadmium reduces growth of male fetuses by impairing development of the placental vasculature and reducing expression of nutrient transporters. PG - 116636 LID - S0041-008X(23)00275-2 [pii] LID - 10.1016/j.taap.2023.116636 [doi] AB - In utero exposure to the toxic metal cadmium (Cd) alters fetoplacental growth in rodents and has been inversely associated with birth weight and infant size in some birth cohorts. Moreover, studies suggest that Cd may have differential effects on growth and development according to offspring sex. The purpose of the current study was to evaluate changes in male and female fetoplacental development following a single injection of saline (5 ml/kg ip) or cadmium chloride (CdCl(2), 2.5, 5 mg/kg, ip) on gestational day (GD) 9. By GD18, no changes in fetal or placental weights were observed after treatment with 2.5 mg/kg CdCl(2). By comparison, the weight and length of male fetuses and their placentas were reduced following treatment with 5 mg/kg CdCl(2) whereas no change was observed in females. In addition, the area of maternal and fetal blood vessels as well as the expression of the glucose transporters, Glut1 and Glut3, and the endothelial marker, CD34, were reduced in the placentas of CdCl(2)-treated male offspring compared to females. Interestingly, the placentas of females accumulated 80% more Cd than males after CdCl(2) (5 mg/kg) administration. Female placentas also had higher concentrations of zinc and the zinc transporter Znt1 compared to males which may explain the limited changes in fetal growth observed following CdCl(2) treatment. Taken together, disruption of vasculature development and reduced expression of glucose transporters in the placenta provide potential mechanisms underlying reduced fetal growth in male offspring despite the greater accumulation of Cd in female placentas. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Kozlosky, Danielle AU - Kozlosky D AD - Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA. FAU - Lu, Alexander AU - Lu A AD - Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA. FAU - Doherty, Cathleen AU - Doherty C AD - Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA.. Electronic address: cld133@eohsi.rutgers.edu. FAU - Buckley, Brian AU - Buckley B AD - Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA.. Electronic address: bbuckley@eohsi.rutgers.edu. FAU - Goedken, Michael J AU - Goedken MJ AD - Research Pathology Services, Rutgers University, Piscataway, NJ 08854, USA.. Electronic address: mg1202@research.rutgers.edu. FAU - Miller, Richard K AU - Miller RK AD - School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY 14642, USA.. Electronic address: RichardK_Miller@URMC.Rochester.edu. FAU - Barrett, Emily S AU - Barrett ES AD - Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA.; School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY 14642, USA.; Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, USA.. Electronic address: esb104@eohsi.rutgers.edu. FAU - Aleksunes, Lauren M AU - Aleksunes LM AD - Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ 08854, USA.; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA.. Electronic address: aleksunes@eohsi.rutgers.edu. LA - eng GR - T32 ES007148/ES/NIEHS NIH HHS/United States GR - P30 ES005022/ES/NIEHS NIH HHS/United States GR - R01 ES029275/ES/NIEHS NIH HHS/United States GR - F31 ES032319/ES/NIEHS NIH HHS/United States GR - UL1 TR003017/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20230722 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 00BH33GNGH (Cadmium) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Pregnancy MH - Female MH - Male MH - Humans MH - *Placenta/metabolism MH - *Cadmium/toxicity/metabolism MH - Fetal Development MH - Fetus MH - Glucose/metabolism PMC - PMC10528997 MID - NIHMS1923683 OTO - NOTNLM OT - Cadmium OT - Fetal growth restriction OT - Fetal sex OT - Placenta OT - Placental vasculature COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lauren Aleksunes reports financial support was provided by National Institute of Environmental Health Sciences. Danielle Kozlosky reports financial support was provided by National Institute of Environmental Health Sciences. Emily Barrett reports financial support was provided by National Institute of Environmental Health Sciences. Lauren Aleksunes reports financial support was provided by National Center for Advancing Translational Sciences. EDAT- 2023/07/25 01:09 MHDA- 2023/08/28 06:43 PMCR- 2024/09/15 CRDT- 2023/07/24 22:01 PHST- 2023/05/23 00:00 [received] PHST- 2023/07/12 00:00 [revised] PHST- 2023/07/21 00:00 [accepted] PHST- 2024/09/15 00:00 [pmc-release] PHST- 2023/08/28 06:43 [medline] PHST- 2023/07/25 01:09 [pubmed] PHST- 2023/07/24 22:01 [entrez] AID - S0041-008X(23)00275-2 [pii] AID - 10.1016/j.taap.2023.116636 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2023 Sep 15;475:116636. doi: 10.1016/j.taap.2023.116636. Epub 2023 Jul 22.