Cullin 7 and Fbxw 8 expression in trophoblastic cells is regulated via oxygen tension: implications for intrauterine growth restriction?

Abstract

OBJECTIVE:

The F-box protein Fbxw8 is a cofactor of Cullin 7 (Cul7), which regulates protein transfer to the proteasome and cell growth. Cul7 or Fbxw8 deficiency is associated with intrauterine growth restriction (IUGR) due to abnormal placental development leading to poor oxygen supply to the fetus. We studied the role of hypoxia for Fbxw8 and Cul7 expression in trophoblastic cells.

METHODS:

Immunomagnetic bead-separated extravillous trophoblast (EVT) and villous trophoblast (VT) and trophoblast cell lines were incubated with 1 or 8% O(2). Fbxw8 and Cul7 expression was determined in IUGR versus matched control placentas.

RESULTS:

Fbxw8 was expressed uniformly in trophoblasts, whereas Cul7 expression was most prominent in trophoblast cell lines. Hypoxia reduced expression of Cul7 and Fbxw8 in all trophoblastic cells, except for villous trophoblasts. In vivo, Cul7 and Fbxw8 were detected in syncytiotrophoblast cells, VT, and EVT cells. Although no significant changes in expression levels of Fbxw8 or Cul7 were noted in IUGR compared with control placentas, Fbxw8 expression correlated negatively with gestational age in the control, but not in the IUGR group.

CONCLUSION:

Fbxw8 and Cul7 expression reveals a complex regulation in trophoblastic cells. Our findings suggest that dysregulation of Cul7 and Fbxw8 expression might affect trophoblast turnover in IUGR.

• Authors: Fabian B Fahlbusch, Yousif Dawood, Andrea Hartner, Carlos Menendez-Castro, Stephanie C Nögel, Anja Tzschoppe, Holm Schneider, Pamela Strissel, Matthias W Beckmann, Ekkehard Schleussner, Matthias Ruebner, Helmuth G Dörr, Ralf L Schild, Wolfgang Rascher, Jörg Dötsch
• Journal: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians (J Matern Fetal Neonatal Med) Vol. 25 Issue 11 Pg. 2209-15 (Nov 2012) ISSN: 1476-4954 [Electronic] England
• PMID: 22524683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CUL7 protein, human
• Cullin Proteins
• F-Box Proteins
• FBXW8 protein, human
• Oxygen

Topics

• Adult
• Cells, Cultured
• Cohort Studies
• Cullin Proteins (genetics, metabolism)
• F-Box Proteins (genetics, metabolism)
• Female
• Fetal Growth Retardation (genetics, metabolism, pathology)
• Gene Expression Regulation (drug effects)
• Gestational Age
• Humans
• Infant, Newborn
• Male
• Oxygen (metabolism, pharmacology)
• Pregnancy
• Trophoblasts (drug effects, metabolism)