{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:18:25Z","timestamp":1787318305818,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Problem<\/jats:title>\n                    <jats:p>Gonadotropin\u2010releasing hormone (GnRH), primarily known for its hypothalamic role in regulating gonadotropin secretion, is also expressed in extra\u2010hypothalamic tissues, including trophoblasts at implantation sites. We investigated the association between trophoblasts and mast cells, demonstrating their role in producing leukemia inhibitory factor (LIF) and matrix metalloproteinase\u20109 (MMP\u20109). Therefore, we hypothesized an additional interaction between trophoblasts and mast cells mediated by GnRH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method of Study<\/jats:title>\n                    <jats:p>Immunohistochemical analysis was conducted to investigate GnRH receptor (GnRHR) expressing mast cell in endometrial and tubal tissues from both pregnant and non\u2010pregnant conditions (2005\u20132018). We established a human mast cell line LAD2 with forced expression of GnRHR expression (GnRHR\u2010expressing LAD2) via lentiviral transfection method. The cells were stimulated with or without leuprorelin (1\u00a0\u00b5M) and transcriptomic analysis and cell migration assays were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GnRHR is expressed in decidual mast cells during uterine pregnancy and in mast cells adjacent to or embedded in trophoblasts of tubal pregnancy. Notably, GnRHR expression was also observed in endometrial mast cells in non\u2010pregnancy conditions. The levels of transcripts encoding LIF, MMP\u20109, and a natural killer (NK) cell attractant C\u2010X\u2010C motif chemokine ligand 16 (CXCL16) were significantly upregulated in GnRHR\u2010expressing LAD2 than in control cells. In addition, culture supernatants from GnRHR\u2010expressing LAD2 cells enhanced the migration of the trophoblast cell line HTR\u20108\/SVneo and the NK cell line NK\u201092 MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that GnRHR expression in mast cells promotes their supportive role in pregnancy establishment by increasing the LIF, MMP\u20109, and CXCL16 productions, recruiting trophoblasts and NK cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.70168","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T18:00:13Z","timestamp":1758218413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Aberrant Expression of Gonadotropin\u2010Releasing Hormone Receptor in Human Mast Cells Enhances the Recruitments of Trophoblasts and NK Cells"],"prefix":"10.1111","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3256-801X","authenticated-orcid":false,"given":"Takashi","family":"Matsuzaki","sequence":"first","affiliation":[{"name":"Department of Pathology Iwate Medical University, Yahaba\u2010cho  Shiwa\u2010gun Iwate Japan"},{"name":"Graduate School of Veterinary Sciences Iwate University  Morioka Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Department of Pathology Iwate Medical University, Yahaba\u2010cho  Shiwa\u2010gun Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1025-5528","authenticated-orcid":false,"given":"Ken R.","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pathology Iwate Medical University, Yahaba\u2010cho  Shiwa\u2010gun Iwate 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