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The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice

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Abstract

The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2–3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.

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Funding

The study was supported by Grant No. DNTS/Russia 02/1/14.06.2018 from the Bulgarian National Science Fund and No. 18-54-18006 from the Russian Foundation for Basic Research.

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Authors and Affiliations

  1. Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str., Bl. 25, 1113, Sofia, Bulgaria

    Yordanka Gluhcheva, Ekaterina Pavlova, Emilia Petrova & Ivelin Vladov

  2. Yaroslavl State University, Sovetskaya Str., 14, Yaroslavl, Russia, 150000

    Alexey A. Tinkov, Olga P. Ajsuvakova, Margarita G. Skalnaya & Anatoly V. Skalny

  3. Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya Str. 6, Moscow, Russia, 117198

    Alexey A. Tinkov, Olga P. Ajsuvakova & Margarita G. Skalnaya

  4. IM Sechenov First Moscow State Medical University, Moscow, Russia, 119146

    Alexey A. Tinkov, Olga P. Ajsuvakova, Margarita G. Skalnaya & Anatoly V. Skalny

  5. Federal Research Centre of Biological Systems and Agro-technologies of the Russian Academy of Sciences, Orenburg, Russia, 460000

    Anatoly V. Skalny

Authors
  1. Yordanka Gluhcheva
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  2. Ekaterina Pavlova
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  8. Anatoly V. Skalny
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Correspondence to Yordanka Gluhcheva.

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This experimental design was carried out in accordance with the guidelines of EU Directive 2010/63/EU for animal experiments. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Gluhcheva, Y., Pavlova, E., Petrova, E. et al. The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice. Biol Trace Elem Res 194, 423–431 (2020). https://doi.org/10.1007/s12011-019-01790-8

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