Preimplantation signalling system discovered in human embryos

Human embryos can show an innate immune response when exposed to pathogens, as early as day five, researchers in the UK have found.

New research conducted by scientists at the University of Manchester and Manchester University NHS Foundation Trust has shown preimplantation human embryos express a protein that detects bacteria and viruses, triggering an immune response and thereby demonstrating innate immunity. These proteins are coded for in our genes which means they are considered part of our 'innate' immune system.

'Early human embryos are highly sensitive to their local environment, however before this study, relatively little was known about how they detect and respond to specific environmental cues,' said Professor Daniel Brison, scientific director at the Department of Reproductive Medicine at Saint Mary's Hospital, Manchester and lead author of the study. He added: 'We already knew that embryos communicate with mum when they begin to implant, but we don't know why this new signaling happens.'

Scientists looked at toll-like receptors (TLRs) which are a class of proteins that play a key role in our immune system. Previous studies have shown that TLRs are expressed in the fallopian tube and vagina.

Published in the journal Human Reproduction, the research team was the first to report expression of the TLR system in human embryos. These findings suggest that the TLR system is active in human embryos and may play a role in inducing an inflammatory response in the maternal tract in response to pathogens, such as bacteria and viruses, or in modulating the implantation and initiating pregnancy.

The team cultured 25 five-day old human embryos in the presence of substances known to trigger a response in TLR receptors, during embryo development up to day six. Gene expression and mRNA profiles were used to confirm that the cells in the embryo had initiated the TLR system immune response.

One reason given by the authors for the study was to ascertain whether 'impurities' that embryos come into contact with when being cultured in vitro for IVF can stimulate immune receptors. They call for future consideration of immunogenicity of cell culture components used in IVF, in light of their findings.

'[Our research] might one day shine a light on infertility: why some embryos do not implant into the uterus or even help us to identify the quality of IVF embryos developing in culture,' said Professor Brison.

The department where this research was conducted carries out IVF on the NHS and was at risk of closure more than a year ago (see BioNews 1044) after the hospital could not afford a £10 million refurbishment.