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

Relaxin-deficiency results in increased angiogenic gene expression in the uterus of early pregnant mice. (#182)

Sarah A Marshall 1 , Laura J Parry 1 , Jane E Girling 2
  1. University of Melbourne, Parkville, VIC, Australia
  2. Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, Victoria, Australia

Impaired vascular adaptation in the uterus during early pregnancy contributes to increased risk of pregnancy complications such as preeclampsia, miscarriage and intrauterine growth restriction. The peptide hormone relaxin reaches peak circulating concentrations at the end of the first trimester in pregnant women, and is thought to promote angiogenesis.  The aim of this study was to investigate the role of relaxin in uterine vascular adaptations during early pregnancy.  We examined the effects of relaxin-deficiency on uterine gene expression in early pregnancy, focusing specifically on angiogenic genes. Quantitative RT-PCR was used to measure gene expression in uterine tissue prior to implantation (days 1-4) in wild type (Rln+/+) and relaxin-deficient mice (Rln-/-).  Gene expression was also quantified in the uteri of Rln-/- mice at day 4 of pregnancy after 3 days of relaxin (0.2μg/μl/hour, Alzet® osmotic minipump) or saline (0.9%) treatment.  Genes analyzed included angiogenic factors (vascular endothelial growth factor-A, VegfA; hypoxia-inducible factor-1α, Hif-1α; egl nine homolog-1, Egln1) and genes involved in extracellular matrix remodeling (matrix metalloproteinase-14, Mmp14; tissue inhibitor of metalloproteinase-3, Timp3).  Other genes included receptors for relaxin (Rxfp1), VEGFA (Vegfr2) and estrogen (Esr1, Esr2). Expression of Egln1, Esr1, Hif-1α, Mmp14, Rxfp1, VegfA and Vegfr2 mRNAwere significantly increased on day 1 of pregnancy in Rln-/- compared to Rln+/+ mice.  By day 4 of pregnancy, differences in mRNA expression were no longer detectable between the genotypes for most genes.  Only VegfA mRNA increased significantly in response to relaxin treatment.  These studies demonstrate that relaxin-deficiency impacts uterine gene expression in early pregnant mice.  We hypothesise that the early increase in angiogenesis-related genes may cause abnormal endometrial endothelial cell proliferation in early mouse pregnancy.  Ongoing studies are now examining the pattern of endometrial endothelial cell proliferation in these animals.