Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Regular and fibroid-associated heavy menstrual bleeding have different endometrial molecular mechanisms (#333)

Jane E Girling 1 , Michelle Lockhart 1 , Moshe Olshansky 2 , Premila Paiva 1 , Martha Hickey 1 , Peter AW Rogers 1
  1. Gynaecology Research Centre, University of Melbourne Department of Obstetrics and Gynaecology, Royal Womens Hospital, Parkville, VIC, Australia
  2. Bioinformatics Division, Walter and Elisa Hall Institute, Parkville, Victoria, Australia

Heavy menstrual bleeding (HMB) is a significant social, medical and public health issue that affects 10-30% of menstruating women.  Our goal is to identify the molecular mechanisms responsible for HMB; the specific aim of this study was to identify gene expression differences in menstrual-phase endometrium from women with HMB of different aetiologies.  We hypothesised that analysis of gene expression in women with regular versus fibroid associated HMB would identify gene pathways with key roles in menstruation.

Menstrual phase endometrial biopsies were collected from women with regular menstrual cycles with/without HMB, or from women with uterine fibroids.  Biopsies were analysed using Illumina Sentrix Human HT12 arrays and data analysed using ‘Remove Unwanted Variation, 4-step’ (RUV4) and RUV-inverse methods. Reactome (pathway database) was used to identify pathways containing differentially expressed genes specific to the different clinical groupings.

Overall, 1199 genes were differentially expressed among different groups.  Of the 55 genes differentially expressed in menstrual endometrium from women with HMB, 6 were associated with signal transduction including 4 chemokines involved in leucocyte recruitment (CCL3L3, CCL4, CCL4L2, CXCL5).  An additional 4 genes were related to haemostasis including genes for the fibrinogen alpha and beta chains (FGA, FGB).  Of the 179 genes differentially expressed in biopsies from women with fibroids, 18 genes were associated with immune function.  This included several genes linked with uterine natural killer cell function (KIR2dL4, KIR2DS5, KIR3DL2, KIR2DL5A, ULBP2, CCL8, MICA).  A further 8 genes were associated with haemostasis.

We now have a promising list of genes linked to HMB which we are currently validating.  We have identified several gene pathways that are significantly different in women with HMB or uterine fibroids.  These include gene pathways related to uterine natural killer cell activity, signal transduction (chemokines) and haemostasis.  Further study of these gene sets may elucidate mechanisms responsible for HMB.