The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Macrophage depletion in the post-implantation phase elicits implantation failure through effects on the ovary and uterus in mice (#378)

Holly M Groome 1 2 , Peck Yin Chin 1 2 , Alison S Care 1 2 , Claire T Roberts 1 2 , Sarah A Robertson 1 2
  1. The University of Adelaide, Adelaide, SA, Australia
  2. The Robinson Research Institute, Adelaide, SA, Australia

Pregnancy is a unique example of immune tolerance where the mother’s immune system is able to tolerate and support the growth and development of the semi-allogeneic fetus. This process is mediated by a range of tolerance-promoting immune cells that suppress inflammation to which can impair placental and fetal development. Macrophages are involved in generating tolerance, as well as maternal tissue remodelling and vascular adaptations required to establish pregnancy. We hypothesised that macrophages are crucial for embryo implantation and placental development. The experiments utilised the CD11b-DTR murine macrophage depletion model wherein CD11b-DTR mice express the monkey diphtheria toxin receptor (DTR) via the CD11b promoter causing transient depletion of CD11b+ cells upon diphtheria toxin (DT) treatment. CD11b-DTR or wild-type FVB females were mated to BALB/c stud males and administered DT on day 5.5 pc. Pregnancy outcomes were then assessed on days 6.5 and 7.5 pc. Pregnancy rate was not altered 24 h post macrophage depletion, however by 48 h viable implantation sites were reduced by 60%. To assess the cause of pregnancy failure, uteri and ovaries were collected and stained to assess morphometric changes. The ovaries from mice treated with DT were significantly impacted with haemorrhagic infiltration in the corpora lutea. There was no change to serum progesterone on day 6.5 but a significant decrease was evident on day 7.5. Furthermore, there were anomalies in the structure of the decidua and reduced vascularisation around implantation sites. In conclusion, macrophage depletion during embryo implantation affects pregnancy rate, corpus luteum structure and potentially the decidual response and neovascularisation around implantation sites. These results add to earlier work demonstrating a key role for macrophages in development of the corpora lutea in the pre-implantation phase, and indicate a crucial role for macrophages in sustaining progression of early pregnancy through effects in both the ovary and uterus.