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Effect of Cadmium on Trophoblast Cell Proliferation and Apoptosis in Different Gestation Periods of Rat Placenta

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Abstract

In this study, we aimed to show how cadmium (Cd) affects the trophoblast proliferation and differentiation in the placenta and the apoptotic activity in different gestational days and, hence, its effects of placental development with immunohistochemical and TUNEL techniques. Experimental model of our study consisted of placental development of control and Cd groups on 15, 17, 19, and 21th days of the gestation. Female rats in Cd groups were subcutaneously administered a single dose of 0.5 mg Cd/kg/day dissolved in sodium chloride as 2 mL/kg Cd chloride until the day they sacrificed. Embryo and placenta of female rats were separately removed on 15, 17, 19, and 21th days of the gestation in which the placental development takes place and placentas were processed for microscopic examinations. In the placentas of the control group, all layers were observed to be formed on the 15th gestational day and thereafter a continuous growth was monitored. In the Cd group also all layers existed from the 15th gestational day. However, they were smaller in size than control groups. Frequency of proliferating cell nuclear antigen (PCNA)-positive cells was decreased and the number of apoptotic cells was increased in all the gestational days related to Cd. In conclusion, Cd administered during the pregnancy was observed to cause abnormal placental development by disrupting the normal structure of the placenta, inhibiting the proliferation of trophoblast and increasing the number of apoptotic trophoblast cells.

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References

  1. Forbes K, Westwood M (2008) The IGF axis and placental function [a mini review]. Horm Res 69(3):129–137

    Article  PubMed  CAS  Google Scholar 

  2. Genbacev O, McMaster MT, Fisher SJ (2000) A repertoire of cell cycle regulators whose expression is coordinated with human cytotrophoblast differentiation. Am J Pathol 157(4):1337–1351

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Waddell BJ, Hisheh S, Dharmarajan AM, Burton PJ (2000) Apoptosis in rat placenta is zone-dependent and stimulated by glucocorticoids. Biol Reprod 63(6):1913–1917

    Article  PubMed  CAS  Google Scholar 

  4. Hikim AP, Wang C, Leung A, Swerdloff RS (1995) Involvement of apoptosis in the induction of germ cell degeneration in adult rats after gonadotropin-releasing hormone antagonist treatment. Endocrinology 136(6):2770–2775

    PubMed  CAS  Google Scholar 

  5. Kippler AM, Hogue AM, Ragib R, Ohrvik H, Ekström EC, Vahter M (2010) Accumulation of cadmium in human placenta interacts with the transport ofmicronutrients to the fetus. Toxicol Lett 192:162–168

    Article  PubMed  CAS  Google Scholar 

  6. World Health Organization (1992) Environmental health criteria, cadmium, vol.134. WHO, Geneva, pp. 92–205

    Google Scholar 

  7. Dechanet C, Anahory T, Mathieu DJ, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H (2011) Effects of cigarette smoking on reproduction. Hum Reprod Update 17:76–95

    Article  PubMed  CAS  Google Scholar 

  8. Aktas C, Kanter M, Erboga M, Ozturk S (2012) Anti-apoptotic effects of curcumin on cadmium-induced apoptosis in rat testes. Toxicol Ind Health 28(2):122–130

    Article  PubMed  CAS  Google Scholar 

  9. Aktoz T, Kanter M, Uz YH, Aktaş C, Erboğa M, Atakan İH (2012) Protective effect of quercetin against renal toxicity induced by cadmium in rats. Balkan Med J 29:56–61

    CAS  Google Scholar 

  10. Alpsoy S, Kanter M, Aktas C, Erboga M, Akyuz A, Akkoyun DC, Oran M (2014) Protective effects of onion extract on cadmium-induced oxidative stress, histological damage, and apoptosis in rat heart. Biol Trace Elem Res 159(1–3):297–303

    Article  PubMed  CAS  Google Scholar 

  11. Kanter M, Unsal C, Aktas C, Erboga M (2013) Neuroprotective effect of quercetin against oxidative damage and neuronal apoptosis caused by cadmium in hippocampus. Toxicol Ind Health. doi:10.1177/0748233713504810

    Google Scholar 

  12. Fahim MA, Nemmar S, Dhanasekaran S, Singh M, Shafiullah J, Yasin J, Zia S, Hasan MY (2012) Acute cadmium exposure causes systemic and thromboembolic events in mice. Physiol Res 61:73–80

    PubMed  CAS  Google Scholar 

  13. Stosic J, Mirkov I, Belij S, Nikolic M, Popov A, Kataranovski D, Kataranovski M (2010) Differences in pulmonary inflammation following systemic cadmium administration in rats. Biomed Environ Sci 23:293–299

    Article  PubMed  CAS  Google Scholar 

  14. Klaassen CD, Bhalchandra JL, Diwan A (2009) Metallothionein protection of cadmium toxicity. YTAAP 238:215–220

    CAS  Google Scholar 

  15. Unsal C, Kanter M, Aktas C, Erboga M (2013) Role of quercetin in cadmium-induced oxidative stress, neuronal damage, and apoptosis in rats. Toxicol Ind Health. doi:10.1177/0748233713486960

    Google Scholar 

  16. Fukase Y, Tsugami H, Nakamura Y, Ohba K, Ohta H (2014) The role of metallothionein and metal transporter on cadmium transport from mother to fetus. Yakugaku Zasshi 134(7):801–804

    Article  PubMed  CAS  Google Scholar 

  17. Nakamura Y, Ohba K, Suzuki K, Ohta H (2012) Health effects of low-level cadmium intake and the role of metallothionein on cadmium-transport from mother rats to fetus. J Toxicol Sci 37:149–156

    Article  PubMed  CAS  Google Scholar 

  18. Soares MJ, Chakraborty D, Karim Rumi MA, Konno T, Renaud SJ (2012) Rat placentation: an experimental model for investigating the hemochorial maternal-fetal interface. Placenta 33:233–243

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Ain R, Konno T, Canham LN, Soares MJ (2006) Phenotypic analysis of the rat placenta. In: Soares MJ, Hunt JS (eds) Placenta and trophoblast methods in molecular medicine. Humana Press Inc., Totowa, pp. 295–313

    Google Scholar 

  20. Nampoothiri LP, Gupta S (2008) Biochemical effects of gestational coexposure to lead and cadmium on reproductive performance, placenta, and ovary. J Biochem Mol Toxicol 22(5):337–344

    Article  PubMed  CAS  Google Scholar 

  21. Zalups RK, Ahmad S (2003) Molecular handling of cadmium in transporting epithelia. Toxicol Appl Pharmacol 186:163–188

    Article  PubMed  CAS  Google Scholar 

  22. IARC International Agency for Research on Cancer (1993) Beryllium, cadmium, mercury and exposures in the glass manufacturing industry 58. IARC, Lyon, pp. 119–238

    Google Scholar 

  23. M del C D, González NV, Gómez S, Quiroga MA, Najle R, Barbeito CG (2014) Effect of a single dose of cadmium on pregnant Wistar rats and their offspring. Reprod Dom Anim 49:1049–1056

    Article  CAS  Google Scholar 

  24. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580

    Article  PubMed  CAS  Google Scholar 

  25. Acar N, Korgun ET, Cayli S, Sahin Z, Demir R, Ustunel I (2008) Is there a relationship between PCNA expression and diabetic placental development during pregnancy? Acta Histochem 110(5):408–417

    Article  PubMed  CAS  Google Scholar 

  26. Schuler-Maloney D (2000) Placental triage of the singleton placenta. JMWH 45(2):104–113

    PubMed  CAS  Google Scholar 

  27. Soares M, Chapman BM, Rasmussen CA, Dai G, Kamei T, Orwig KE (1996) Differentiation of trophoblast endocrine cells. Placenta 17:277–289

    Article  PubMed  CAS  Google Scholar 

  28. Ma GT, Solovena V, Tzeng S-J, Lowe LA, Pfendler KC, Iannaccone PM, Kuehn MR, Linzer DIH (2001) Nodal regulates trophoblast differentiation and placental development. Dev Biol 236:124–135

    Article  PubMed  CAS  Google Scholar 

  29. Malassiné A, Frendo JL, Evain-Brion D (2003) A comparison of placental development and endocrine functions between the human and mouse model. Hum Reprod Update 9:531–539

    Article  PubMed  Google Scholar 

  30. Ain R, Canham LN, Soares MJ (2003) Gestation stage-dependent intrauterine trophoblast cell invasion in the rat and mouse: novel endocrine phenotype and regulation. Dev Biol 260:176–190

    Article  PubMed  CAS  Google Scholar 

  31. Soares MJ (2004) The prolactin and growth hormone families: pregnancy-specific hormones/cytokines at the maternal-fetal interface. Reprod Biol Endocrinol 2:51–66

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. He Y, Smith SK, Day KA, Clark DE, License DR, Charnock-Jones DS (1999) Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT−1) premRNA is important for the regulation of VEGF activity. Mol Endocrinol 13:537–545

    Article  PubMed  CAS  Google Scholar 

  33. Kuhnert BR, Kuhnert PM, Erhard P, Brashear WT, Groh-Wargo SL, Webster S (1987) The effect of smoking on placental and fetal zinc status. Am J Obstet Gynecol 157:1241–1246

    Article  PubMed  CAS  Google Scholar 

  34. Osman K, Akesson A, Berglund M, Bremme K, Schütz A, Ask K, Vahter M (2000) Toxic and essential elements in placentas of Swedish women. Clin Biochem 33(2):131–138

    Article  PubMed  CAS  Google Scholar 

  35. Philip RB (1995) Environmental hazards and human health. CRC Lewis Publishers Boca Raton, Florida

    Google Scholar 

  36. Elinder CG, Kjellstrom T, Lind B, Linnman L, Piscator M, Sundstedt K (1983) Cadmium exposure from smoking cigarettes. Variations with time and country where purchased. Environ Res 32:220–227

    Article  PubMed  CAS  Google Scholar 

  37. Schoeters G, Den Hond E, Zuurbier M, Naginiene R, van den Hazel P, Stilianakis N, Ronchetti R, Koppe JG (2006) Cadmium and children: exposure and health effects. Acta Paediatr Suppl 95(453):50–54

    Article  PubMed  Google Scholar 

  38. Whelton BD, Bhattacharyya MH, Carnes BA, Moretti ES, Peterson DP (1998) Female reproduction and pup survival and growth for mice fed a cadmium-containing purifıed diet through six consecutive rounds of gestation and lactation. J Toxicol Environ Health 24:321–343

    Article  Google Scholar 

  39. Kostial K, Blanusa M, Schönwald N, Arezina R, Piasek M, Jones MM, Singh PK (1993) Organ cadmium deposits in orally exposed female rats and their pups and the depleting efficiency of sodium N-4-(methoxybenzyl)-d-glucamine-N-carbodithioate monohydrate (MeOBDCG). Appl Toxicol 13:203–207

    Article  CAS  Google Scholar 

  40. Huel G, Everson RB, Menger I (1984) Increased hair cadmium in newborns of women occupationally exposed to heavy metals. Environ Res 35:115–121

    Article  PubMed  CAS  Google Scholar 

  41. Huel G, Boudene C, Ibrahim MA (1981) Cadmium and lead content of maternal and newborn hair: relationship to parity, birth weight, and hypertension. Arch Environ Health 36:221–227

    Article  PubMed  CAS  Google Scholar 

  42. Kuhnert B, Kuhnert PM, Zarlingo TJ (1988) Associations between placental cadmium and zinc and age and parity in pregnant woman who smoke. Obstet Gynecol 71(1):67–70

    PubMed  CAS  Google Scholar 

  43. Yoruk M, Kanter M, Meral I (2003) Localization of glycogen in the placenta and fetal and maternal livers of cadmium-exposed diabetic pregnant rats. Biol Trace Elem Res 96(1–3):217–226

    Article  PubMed  CAS  Google Scholar 

  44. Kanter M, Yoruk M, Koc A, Meral I, Karaca T (2003) Effects of cadmium exposure on morphological aspects of pancreas, weights of fetus and placenta in streptozotocin-induced diabetic pregnant rats. Biol Trace Elem Res 93(1–3):189–200

    Article  PubMed  CAS  Google Scholar 

  45. Maruo T, Ishihara N, Samoto T, Murakoshi H, Laoag-Fernandez JB, Matsuo H (2001) Regulation of human trophoblast proliferation and apoptosis during pregnancy. Early Pregnancy 5(1):28–29

    PubMed  CAS  Google Scholar 

  46. Unek G, Ozmen A, Kipmen-Korgun D, Korgun ET (2012) Immunolocalization of PCNA, Ki67, p27 and p57 in normal and dexamethasone-induced intrauterine growth restriction placental development in rat. Acta Histochem 114(1):31–40

    Article  PubMed  CAS  Google Scholar 

  47. Attanasio A, Schiffer D (1990) Ultrastructural detection of DNA strand breaks by in situ end-labelling techniques. J Pathol 176:27–35

    Google Scholar 

  48. Erel CT, Dane B, Calay Z, Kaleli S, Aydinli K (2001) Apoptosis in the placenta of pregnancies complicated with IUGR. Int J Gynecol Obstet 73:229–235

    Article  CAS  Google Scholar 

  49. Ejima K, Koji T, Tsuruta D, Nanri H, Kashimura M, Ikeda M (2000) Induction of apoptosis in placentas of pregnant mice exposed to lipopolysaccharides: possible involvement of Fas/Fas ligand system. Biol Reprod 62:178–185

    Article  PubMed  CAS  Google Scholar 

  50. Doi K, Ishigami N, Sehata S (2008) T-2 toxin-induced toxicity in pregnant mice and rats. Int J Mol Sci 9:2146–2158

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Furukawa S, Usuda K, Abe M, Hayashi S, Ogawa I (2007) Busulfan-induced apoptosis in rat placenta. Exp Toxicol Pathol 59:97–103

    Article  PubMed  CAS  Google Scholar 

  52. Katayama K, Ueno M, Takai H, Ejiri N, Uetsuka K, Nakayama H, Doi K (2002) Ethylnitrosourea induced apoptosis and growth arrest in the trophoblastic cells of rat placenta. Biol Reprod 67:431–435

    Article  PubMed  CAS  Google Scholar 

  53. Yamauchi H, Katayama K, Ueno M, Uetsuka K, Nakayama H, Doi K (2004) Involvement of p53 in 1-b-D-arabinofuranosylcytosine-induced trophoblastic cell apoptosis and impaired proliferation in rat placenta. Biol Reprod 70:1762–1767

    Article  PubMed  CAS  Google Scholar 

  54. Chauhan M, Yallampalli U, Reed L, Yallampalli C (2006) Adrenomedullin antagonist infusion to rats during midgestation causes fetoplacental growth restriction through apoptosis. Biol Reprod 75(6):940–947

    Article  PubMed  CAS  Google Scholar 

  55. Antipatis C, Ashworth CJ, Riley SC, Hannah L, Hoggard N, Lea RG (2002) Vitamin A deficiency during rat pregnancy alters placental TNF-α signalling and apoptosis. Am J Reprod Immunol 47(3):151–158

    Article  PubMed  Google Scholar 

  56. Katayama K, Ueno M, Takai H, Ejiri N, Uetsuka K, Nakayama H, Doi K (2002) Ethylnitrosourea induces apoptosis and growth arrest in the trophoblastic cells of rat placenta. Biol Reprod 67(2):431–435

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Histology and Embryology, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey

    Mustafa Erboga

  2. Department of Histology and Embryology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey

    Mehmet Kanter

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  1. Mustafa Erboga
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  2. Mehmet Kanter
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Correspondence to Mustafa Erboga.

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Erboga, M., Kanter, M. Effect of Cadmium on Trophoblast Cell Proliferation and Apoptosis in Different Gestation Periods of Rat Placenta. Biol Trace Elem Res 169, 285–293 (2016). https://doi.org/10.1007/s12011-015-0439-8

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  • DOI: https://doi.org/10.1007/s12011-015-0439-8

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