INTRODUCTION: Small ubiquitin-like modifiers (SUMO) conjugate to target proteins 
in a dynamic, reversible manner to function as post-translational modifiers. 
SUMOylation of target proteins can impinge on their localization, in addition to 
their activity or stability. Differential expression of deSUMOylating enzymes 
(SENP 1 and 2) contributes to altered mammalian placental development and 
function in mice. Severe preeclampsia (sPE) is associated with abnormal 
placental development and chronic ischemic injury. Extra- and intracellular 
stimuli/stressors that include hypoxic-activated pathways are known modulators 
of SUMOylation. In this current study we hypothesized that placentas from sPE 
patients will display up regulation in the SUMO regulatory pathway.
METHODS: Utilizing qRT-PCR, immuno-blotting and Western techniques, we 
determined the expression levels of SUMO pathway genes in healthy and diseased 
placentas. We also exposed placental explants to hypoxia to study the effect on 
the SUMOylation pathway.
RESULTS: We observed steady-state expression of SUMO1-3, SUMO-conjugated 
enzyme-UBC9 and deSUMOylating enzymes - SENPs, throughout normal gestation. An 
elevated level of free SUMO1-3 and SUMO-protein conjugates was observed in sPE 
placentas. Furthermore, placental UBC9 levels were strikingly increased in the 
same sPE patients. Hypoxia-induced SUMOylation in first trimester placental 
explants.
DISCUSSION: Our data demonstrate an elevated steady-state of SUMOylation in sPE 
placentas compared with gestational aged-matched controls. The observed 
hyper-SUMOylation in sPE placentas correlates with elevated expression of UBC9 
rather than with reduced expression of SENPs Hypoxia may contribute to 
alterations in placental SUMOylation pathway.
CONCLUSION: Increased placental SUMOylation may contribute to the pathogenesis 
of serious placental pathology that causes extreme preterm birth.