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Estrous cycles of heifers were synchronized, followed by either a sham procedure (n\u2009=\u200915) or embryo transfer (n\u2009=\u200971) on day 7 (day 1\u2009=\u2009ovulation). Endometrial luminal epithelial cells were collected, and luteal function was assessed via Doppler ultrasonography on days 6, 15, and 20. Animals were categorized into five groups (n\u2009=\u20096\u20138\/group): cycling (simulated embryo transfer), EL7-20, EL20-25, EL25-30 (embryo losses detected on days 20, 25, or 30, respectively), and pregnant (confirmed by day 30). Endometrial ISG15 and RSAD2 expression was upregulated in EL20\u201325, EL25\u201330, and pregnant groups on days 15 and 20, indicating conceptus-induced immune activation in heifers with maintained corpora lutea. IRF2 was downregulated on day 15 in the EL25\u201330 and pregnant group. On day 20, IFN\u03b3, IL6, and IL10 were upregulated in EL20\u201325, EL25\u201330, and pregnant groups, reflecting immune modulation supportive of pregnancy, whereas IL1\u03b2 and IL8 were increased only in EL20\u201325 and EL25\u201330 groups, indicating a pro-inflammatory state associated with pregnancy loss. TGF\u03b21 expression increased on day 20 in cycling and EL7\u201320 groups. TLR2 expression increased between days 6 and 20 in pregnant, EL20\u201325, and EL25\u201330 groups, while TLR4 was dysregulated across all groups except pregnant. These findings indicate that the conceptus stimulates early immune activation\u2014characterized by the induction of interferon-stimulated genes, IL6, IL10, IFN\u03b3, and TLR2\u2014by day 15 in recipients with sustained luteal activity, independent of pregnancy outcomes. In contrast, dysregulated IL1\u03b2, IL8, and TLR4 expression is associated with early pregnancy failure.<\/jats:p>","DOI":"10.1093\/reprod\/xaaf011","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:01:44Z","timestamp":1768467704000},"source":"Crossref","is-referenced-by-count":0,"title":["Dynamic of interferon signaling and immune regulation in the bovine endometrium during successful and failed pregnancies"],"prefix":"10.1093","volume":"171","author":[{"given":"Samuel Volpe","family":"Souza","sequence":"first","affiliation":[{"name":"Department of Animal Reproduction, University of S\u00e3o Paulo , Pirassununga, SP, 13635-900,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9747-9385","authenticated-orcid":false,"given":"Isabella","family":"Rio Feltrin","sequence":"additional","affiliation":[{"name":"Department of Animal Reproduction, University of S\u00e3o Paulo , Pirassununga, SP, 13635-900,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago Neder","family":"Lisboa","sequence":"additional","affiliation":[{"name":"Department of Animal Reproduction, University of S\u00e3o Paulo , Pirassununga, SP, 13635-900,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabrielle Ceragioli","family":"Damaceno","sequence":"additional","affiliation":[{"name":"Department of Animal Reproduction, University of S\u00e3o Paulo , Pirassununga, SP, 13635-900,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Karolyne Alves","family":"Miguel","sequence":"additional","affiliation":[{"name":"Department of Animal Reproduction, University of S\u00e3o Paulo , Pirassununga, SP, 13635-900,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda Guimar\u00e3es","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Animal Reproduction, University of S\u00e3o Paulo , Pirassununga, SP, 13635-900,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas Carnio de Siqueira","family":"Branco","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, Southwest Research, Extension, and Education Center, University of Missouri, Mt Vernon, 65712,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelyane Jos\u00e9","family":"Lopes","sequence":"additional","affiliation":[{"name":"Genus, ABS , Mogi Mirim, SP, 13.800-478,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago Fernandes","family":"Amaral","sequence":"additional","affiliation":[{"name":"Genus, ABS , Mogi Mirim, SP, 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