Determination of PCNA, cyclin D3, p27, p57 and apoptosis rate in normal and dexamethasone-induced intrauterine growth restricted rat placentas

Acta Histochem. 2015 Mar;117(2):137-47. doi: 10.1016/j.acthis.2014.11.010. Epub 2015 Jan 13.


Intrauterine growth restriction (IUGR) is a major clinical problem, which causes perinatal morbidity and mortality. One of the reasons for IUGR is abnormal placentation. In rats, fetal-placental exposure to maternally administered glucocorticoids decreases birth weight and placental weight. Proper placental development depends on the proliferation and differentiation of trophoblasts. Our knowledge about the mitotic regulators that play key roles in synchronizing these events is limited. Also the mechanisms underlying the placental growth inhibitory effects of glucocorticoids have not been elucidated. The aim of this study was to investigate the immunolocalization, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin D3, p27 and p57 in normal and dexamethasone-induced IUGR Wistar rat placentas by reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and Western blot. We also compared apoptotic cell numbers at the light microscopic level via terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) and transmission electron microscopy. Glucocorticoid levels were higher in IUGR rats than in control rats after 60 and 120min of injection. We showed reduced gene and protein expressions of PCNA and cyclin D3 and increased expressions of p27 and p57 in IUGR placentas compared to control placentas. Apoptotic cell number was higher in the placentas of the IUGR group. In brief we found that maternal dexamethasone treatment led to a shift from cell proliferation to apoptosis in IUGR placentas. Dexamethasone induced placental and embryonal abnormalities which could be associated with reduced expressions of PCNA and cyclin D3, increased expressions of p27 and p57 and increased rate of apoptosis in IUGR placentas.

Keywords: Apoptosis; Cyclin D3; PCNA; Rat placenta; p27; p57.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects*
  • Anti-Inflammatory Agents / pharmacology
  • Apoptosis / drug effects*
  • Cyclin D3 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p57 / metabolism*
  • Dexamethasone / adverse effects*
  • Dexamethasone / pharmacology
  • Female
  • Fetal Growth Retardation* / chemically induced
  • Fetal Growth Retardation* / metabolism
  • Fetal Growth Retardation* / pathology
  • Placenta* / metabolism
  • Placenta* / pathology
  • Pregnancy
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Rats
  • Rats, Wistar


  • Anti-Inflammatory Agents
  • Ccnd3 protein, rat
  • Cdkn1b protein, rat
  • Cyclin D3
  • Cyclin-Dependent Kinase Inhibitor p57
  • Proliferating Cell Nuclear Antigen
  • Cyclin-Dependent Kinase Inhibitor p27
  • Dexamethasone