Pre-implantation non-steroidal anti-inflammatory drug treatment disrupts mouse embryo spacing and post-implantation chamber morphogenesis.

Non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit the prostaglandin synthase (PTGS) enzymes PTGS1 and PTGS2, may present a risk when consumed during early pregnancy. The impact of PTGS enzyme inhibition by NSAIDS on the three-dimensional organization and function of uterine compartments in context of implantation success is not well known. Here we show that pre-implantation treatment of mouse pregnancy with indomethacin, an NSAID that inhibits both PTGS1 and PTGS2, results in embryo crowding, delayed embryo implantation, defective implantation chamber formation that eventually results in significant pregnancy loss. These effects are dose dependent as lower doses of indomethacin do not show these effects on pregnancy. When embryo spacing defects were observed, a significant proportion of embryos that showed delayed growth or resorption were located in distinct decidual sites, suggesting that additional mechanisms beyond spatial distribution are at play. These findings highlight the potential risks associated with NSAID use during early pregnancy and underscore the need for further research into the underlying molecular mechanisms and the development of safer pain management strategies during pregnancy.