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Embryo biosensing by uterine natural killer cells determines endometrial fate decisions at implantation
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Kong, Chow-Seng, Ordoñez, Alexandra Almansa, Turner, Sarah, Tremaine, Tina, Muter, Joanne, Lucas, Emma S., Salisbury, Emma, Vassena, Rita, Tiscornia, Gustavo, Fouladi-Nashta, Ali, Hartshorne, Geraldine M., Brosens, Jan J. and Brighton, Paul (2021) Embryo biosensing by uterine natural killer cells determines endometrial fate decisions at implantation. The FASEB Journal, 35 (4). e21336. doi:10.1096/fj.202002217R
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Official URL: https://doi.org/10.1096/fj.202002217R
Abstract
Decidualizing endometrial stromal cells (EnSC) critically determine the maternal response to an implanting conceptus, triggering either menstruation-like disposal of low-fitness embryos or creating an environment that promotes further development. However, the mechanism that couples maternal recognition of low-quality embryos to tissue breakdown remains poorly understood. Recently, we demonstrated that successful transition of the cycling endometrium to a pregnancy state requires selective elimination of pro-inflammatory senescent decidual cells by activated uterine natural killer (uNK) cells. Here we report that uNK cells express CD44, the canonical hyaluronan (HA) receptor, and demonstrate that high-molecular weight HA (HMWHA) inhibits uNK cell-mediated killing of senescent decidual cells. By contrast, low-molecular weight HA (LMWHA) did not attenuate uNK cell activity in co-culture experiments. Killing of senescent decidual cells by uNK cells was also inhibited upon exposure to medium conditioned by IVF embryos that failed to implant, but not successful embryos. Embryo-mediated inhibition of uNK cell activity was reversed by recombinant hyaluronidase 2 (HYAL2), which hydrolyses HMWHA. We further report a correlation between the levels of HYAL2 secretion by human blastocysts, morphological scores, and implantation potential. Taken together, the data suggest a pivotal role for uNK cells in embryo biosensing and endometrial fate decisions at implantation.
| Item Type: | Journal Article | |||||||||||||||||||||||||||
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| Subjects: | Q Science > QR Microbiology R Medicine > RG Gynecology and obstetrics |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Killer cells, Aging | |||||||||||||||||||||||||||
| Journal or Publication Title: | The FASEB Journal | |||||||||||||||||||||||||||
| Publisher: | Federation of American Societies for Experimental Biology | |||||||||||||||||||||||||||
| ISSN: | 0892-6638 | |||||||||||||||||||||||||||
| Official Date: | April 2021 | |||||||||||||||||||||||||||
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| Volume: | 35 | |||||||||||||||||||||||||||
| Number: | 4 | |||||||||||||||||||||||||||
| Article Number: | e21336 | |||||||||||||||||||||||||||
| DOI: | 10.1096/fj.202002217R | |||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||
| Funder: | Tommy’s National Miscarriage Research Centre, Wellcome Trust, WPH Charitable Trust , UHCW NHS Trust, Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia, Torres Quevedo Program of the Spanish Ministry of Science and Innovation, Clinica Eugin intramural funding | |||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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