The Pregnancy Zone Protein (PZP) is significantly downregulated in the placenta of preeclampsia and HELLP syndrome patients

J Reprod Immunol. 2022 Sep:153:103663. doi: 10.1016/j.jri.2022.103663. Epub 2022 Jul 9.

Abstract

Preeclampsia is characterized by maternal hypertension and multi-organ injury. Elongation factor Tu GTP binding domain containing 2 (EFTUD 2) and the Pregnancy Zone Protein (PZP) seem to be important immunomodulatory factors in early gestation. Little is known about the role of EFTUD2 and PZP in disorders of late pregnancy like preeclampsia, HELLP syndrome and intrauterine growth restriction (IUGR). PZP, EFTUD2 and hCG expression was investigated by immunohistochemistry in the placenta of healthy pregnancies (n = 13), preeclampsia (n = 11), HELLP syndrome (n = 12) and IUGR (n = 8). Correlation analysis of protein expression was performed via Spearman correlation coefficient. The characterization of EFTUD2 and PZP expressing cells was evaluated by double-immunofluorescence. After cultivation of the chorion carcinoma cell line BeWo with hCG the expression of PZP and EFTUD2 was investigated by immunocytochemistry. PZP expression was significantly downregulated in the syncytiotrophoblast (ST) and extravillous trophoblast (EVT) of preeclampsia (ST: p 0.001, EVT:p = 0.019) and HELLP syndrome (ST: p = 0.004, EVT: p = 0.035). The expression of EFTUD2 was significantly lower in preeclampsia (ST: p = 0.003, EVT: p 0.001), HELLP syndrome (ST: p = 0.021, EVT: = 0.001, EVT: p = 0.001). EVTs were identified as EFTUD2 and PZP expressing cells by double-immunofluorescence. Stimulation of BeWo chorion carcinoma cells with hCG 1000 IU/mL for 48 h resulted in a significant upregulation of PZP expression (p = 0.027). Our results indicate that PZP and EFTUD2 might be involved in the development of placental dysfunction in preeclampsia and HELLP syndrome.

Keywords: EFTUD2; HELLP syndrome; IUGR; PZP; Preeclampsia.

MeSH terms

  • Carcinoma* / pathology
  • Female
  • Fetal Growth Retardation
  • Guanosine Triphosphate / metabolism
  • HELLP Syndrome*
  • Humans
  • Peptide Elongation Factor Tu / metabolism
  • Peptide Elongation Factors / metabolism
  • Placenta / pathology
  • Pre-Eclampsia* / pathology
  • Pregnancy
  • Pregnancy Proteins / metabolism*
  • Ribonucleoprotein, U5 Small Nuclear / metabolism*

Substances

  • EFTUD2 protein, human
  • PZP protein, human
  • Peptide Elongation Factors
  • Pregnancy Proteins
  • Ribonucleoprotein, U5 Small Nuclear
  • Guanosine Triphosphate
  • Peptide Elongation Factor Tu