Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Seminal plasma TGFβ induces VEGF signalling in the female reproductive tract in the peri-conception period (#52)

Hon Y Chan 1 , John E Schjenken 1 , Sarah A Robertson 1
  1. Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA, Australia

Seminal plasma contains signalling agents such as transforming growth factor-beta (TGFβ) that in mice and other mammals, induce endometrial cytokines and chemokines which contribute to immune adaptation for pregnancy and reproductive success. Whether seminal fluid affects the vascular changes that facilitate embryo implantation has not been investigated, but seems possible given the immune cells recruited by seminal plasma can produce vascular endothelial growth factor (VEGF), which promotes blood vessel growth and formation. We postulated that seminal fluid factors may regulate VEGF family members during the peri-conception period. Vegf expression was measured by qPCR in the endometrium of virgin C57Bl/6 (B6) or B6xCBA (CBAF1) females, or the same females mated with intact, vasectomised (VAS), seminal-vesicle-deficient (SVX) or SVX/VAS BALB/c males (n=16 per group) collected either 8 hours(h) post-coitus(pc) or on day(d) 3.5pc and bioinformatics analysis was completed on existing data sets. At 8h pc, Vegfa expression was significantly induced to the same level following coitus with both intact and VAS males compared to unmated females, suggesting seminal plasma was responsible for its induction. Further, Vegf signalling pathways were highly predicted to be activated following seminal fluid exposure using bioinformatics analysis. However, on d3.5pc Vegfa expression was not altered compared to unmated control. Vegfb, Vegfc and Vegfd were significantly induced in all groups including the SVX/VAS-mated females suggesting that hormonal changes not seminal plasma exposure was responsible for their induction. Given that TGFβ regulates VEGF in other tissues, an in vitro uterine epithelial cell (UEC) culture model was used to assess regulation of VEGF expression. Addition of TGFβ to mouse UEC resulted in a dose dependent increase in VEGF secretion. We conclude that female tract VEGF signalling during the peri-conception period is induced by the seminal plasma signalling molecule, TGFβ, but VEGF is expressed at implantation irrespective of prior seminal fluid contact.