Changes in the plasma microvesicle proteome during the ovarian hyperstimulation phase of assisted reproductive technology

Abstract

The incidence of pulmonary and venous thromboembolism is increased during the first trimester of pregnancies after assisted reproductive technology (ART) compared to spontaneous conception. We previously found that haemostatic plasma variables changed but within normal limits during controlled ovarian hyperstimulation (COH) concomitant with a major increase in plasma microvesicles (MVs) and markers indicating cell activation. We now explored the proteome of these MVs. Thirty-one women undergoing ART were blood sampled at down-regulation (DR) of oestrogen and at high level stimulation (HLS) with its 10-100-fold increased oestrogen level. Samples were analysed by liquid chromatography and tandem mass spectrometry to identify and quantify the proteome. We identified 306 proteins in the MVs and 72 had changed significantly at HLS compared to DR and more than 20% of them were associated with haemostasis. Thus, proteins related to both haemostasis and complement activation altered in plasma MVs in parallel with MV activation during COH. This needs to be further explored in the clinical context.

Figure 1

Volcano plot of all proteins (n = 306) and their change during controlled ovarian hyperstimulation. The x-axis represents the logarithm to the base 2 of the fold change (FC) and the y-axis the negative logarithm of the adjusted P-value. Dotted line demarks the significance level P < 0.01.

Figure 2

Protein-to-protein interaction showing in red colour the proteins identified as blood microvesicle-bound (n = 162 of 206 recognized). The network diagram was originally obtained with STRING database.

Figure 3

Coagulation and complement cascade proteins significantly altered (P < 0.01) during controlled ovarian hyperstimulation (n = 18). Red denotes up-regulated proteins. Blue denotes down-regulated proteins. The diagram was originally obtained from the KEGG database.