Paternal Antigens, Maternal Killer Lymphocytes, and Reproduction
Lead Research Organisation:
Babraham Institute
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
During pregnancy, the developing foetus expresses paternal surface antigens, yet it is normally not recognized by the mother as a foreign tissue graft and is not rejected. Instead the maternal immune system is 'reprogrammed' during pregnancy and is tolerant towards the foetus. This project investigates how maternal immune cells and foetal cells of the placenta interact on the molecular level to achieve a mutually beneficial partnership between mother and foetus that is essential for the success of pregnancy.
Planned Impact
unavailable
Organisations
Publications
Brighton PJ
(2017)
Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium.
in eLife
Hemberger M
(2013)
Immune balance at the foeto-maternal interface as the fulcrum of reproductive success.
in Journal of reproductive immunology
Hemberger M
(2012)
Health during pregnancy and beyond: Fetal trophoblast cells as chief co-ordinators of intrauterine growth and reproductive success.
in Annals of medicine
Hemberger M
(2011)
Reply to Lenz: Parental MHC disparity may affect offspring fitness via uterine natural killer cells
in Proceedings of the National Academy of Sciences
Krueger F
(2009)
Down-regulation of Cdx2 in colorectal carcinoma cells by the Raf-MEK-ERK 1/2 pathway.
in Cellular signalling
Madeja Z
(2011)
Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth.
in Proceedings of the National Academy of Sciences of the United States of America
Ng RK
(2008)
Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5.
in Nature cell biology
Turco MY
(2017)
Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.
in Nature cell biology
Woods L
(2017)
Decidualisation and placentation defects are a major cause of age-related reproductive decline.
in Nature communications
| Description | Pregnancy is a biological paradox, as the developing fetes carries half its genes from the father and should therefore be recognised by the mother as "foreign", similar to a tissue transplant. However, the foeto-maternal interface has developed unique strategies that prevent rejection of foetal-derived placental cells, i.e. those cells that are in direct contact with maternal tissue and blood and carry the father's surface antigens. In this study we have characterised the unique repertoire of paternal antigens expression on placental cells, and show that it is very unusual and different from other somatic cells. This will help the placental cells escape immune recognition. At the same time we demonstrate, however, that a low-level of maternal immune cell activation is essential for a normal, successful pregnancy. It is thus all about getting the balance right. The impact of this work is very high for the clinic; it underpins why specific combinations of immune cell receptors and placental surface antigens are incompatible and don't allow a pregnancy, or lead to severe pregnancy complications such as pre-eclampsia in a proportion of couples. Increased research capacity due to in-depth training of postdoctoral scientist. This work led to her appointment as an Associate Professor at the University of Poznan, Poland. |
| Exploitation Route | This work is carried forward by our collaborators at the university of Cambridge who are investigating pregnancy disorders in humans for such detrimental antigen-receptor mismatches. |
| Sectors | Healthcare |
| Description | Investigating women with a history of recurrent miscarriage or other pregnancy complications for their specific immune cell receptor repertoire, in conjunction with that of the father. |
| Sector | Healthcare |
| Impact Types | Societal |
| Description | School visit |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | presented basic research topic (intrauterine development and essential function of placenta) to primary school children awareness and excitement of young people for science |
| Year(s) Of Engagement Activity | 2006,2007,2008,2009,2010 |
| Description | School's Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | provided basic explanation of early development and the importance of the placenta for growth of a baby; hands-on experience for students in staining and microscopic analysis of a mouse placenta rose awareness of research activities and importance of basic research to understand common pregnancy-associated diseases |
| Year(s) Of Engagement Activity | 2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016 |