Uterine spiral arteries are remodelled in early pregnancy to supply sufficient maternal blood to the developing fetus. Inadequate remodelling is associated with the pregnancy pathologies pre-eclampsia and fetal growth restriction. Maternal natural killer cells within the decidua (dNK cells) are located near spiral arteries while remodelling events, such as disruption and loss of vascular cells and the extracellular matrix, occur. The effect of soluble factors produced by dNK cells on vascular smooth muscle cell (VSMC) apoptosis, differentiation status and matrix disruption was investigated to elucidate how dNK cells may contribute to the remodelling process. Microarray analysis was carried out to determine VSMC gene activity in response to dNK cell secreted factors. First trimester dNK cells were isolated from decidual tissue collected from surgical terminations of pregnancy and cultured to generate conditioned medium (CM) . Prior to termination, uterine artery Doppler ultrasound was carried out as a proxy measure for the extent of spiral artery remodelling. Pregnancies with a high resistance index (RI) are at increased risk of pre-eclampisa; therefore, comparisons were made between dNK cells isolated from women with a High RI and those with a Normal RI. The present study demonstrated that dNK CM does not induce VSMC apoptosis, nor does it alter susceptibility to apoptotic stimuli or VSMC differentiation status. Using a 3- dimensional vascular co-culture assay, it was established that dNK CM does not influence VSMC-mediated disruption of collagen. Decidual NK cells from High RI and Normal RI pregnancies behaved in a similar manner. Microarray analysis and verification identified an increase in interleukin-8 gene expression in VSMC stimulated with dNK CM, consistent with established roles for dNK cell secreted factors in trophoblast recruitment. In conclusion, soluble factors produced by dNK cells do not directly mediate the VSMC changes investigated here, but may alter VSMC production of chemoattractants.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:676100 |
| Date | January 2015 |
| Creators | Host, Amanda J. |
| Publisher | St George's, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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