Cytokines in reproductive pathophysiology
Our research focuses on the role of cytokines in reproductive function, particularly in regulating oocyte maturation and preimplantation embryo development (Figure 1). We are also interested in their determining uterine receptivity in the establishment of pregnancy.
Dysfunctional cytokine-mediated inflammatory responses underlie reproductive disorders, including infertility, pre-eclampsia and preterm labour. We are investigating these disorders in terms of cytokine network regulation, an approach which accounts for the synergistic interactions of these glycoproteins. We are also developing bioinformatic models of these interactions (Dr West) and investigating the role of post-transcriptional regulation of cytokine gene expression in relation to protein levels (Dr Hughes).
Timely regulation of cytokine localisation within the fetoplacental unit (Figure 2) is also central to gestational viability and labour. Alterations in local immune function result in various obstetric complications, which accounts for our investigations into the role of HLA-C and KIR interactions in preeclampsia, fetal growth restriction and miscarriage. Our group is central to several large international studies building on this work into the genetics of pregnancy pathology.
Our routine profiling of cytokine signatures has enabled us to extend this approach to other areas, including cardiovascular research, transplantation biology (Prof Homer-Vanniasinkam) and paediatric leukaemia (Dr Kinsey).
Figure 1.
Figure 2.
GOPEC-consortium. Disentangling fetal and maternal susceptibility for pre-eclampsia: a British multicenter candidate-gene study. Am J Hum Genet 2005;77:127-31.
Orsi NM, Ekbote UV, Walker JJ, Gopichandran N. Uterine and serum cytokine arrays in the mouse during estrus Anim Reprod Sci 2007; 100:301-10
Gopichandran N, Ekbote UV, Walker JJ, Brooke D, Orsi NM. Multiplex determination of murine seminal fluid cytokine profiles. Reproduction 2006; 131:613-21.