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Their evolutionary trajectory is reflected in their expression patterns and diverse functions in embryo implantation, trophoblast invasion, and maternal immune and vascular adaptation, contributing to healthy placentation and uncomplicated pregnancy. Galectin-1 (gal-1), one of the most ancient galectins, plays a pivotal role in feto-maternal immune regulation, acting predominantly from the maternal side to promote immune tolerance, a function integrated early in placental mammalian evolution. In contrast, anthropoid primates introduced a unique set of fetal (placental) galectins (gal-13, gal-14, and gal-16) through birth-and-death evolution, with these genes localized on human chromosome 19. Notably, these primate species have evolved varying degrees of deep placentation, with humans exhibiting the deepest, which facilitates enhanced nutrient delivery to the fetus, particularly for brain development. Placental galectins have been implicated in the evolution of immune tolerance mechanisms that support deep placentation. During pregnancy, reduced expression of maternal galectins (e.g., gal-1) and placental galectins (e.g., gal-13) has been associated with severe obstetric complications, signaling disruptions in feto-maternal tolerance. This review provides a comprehensive overview of gal-1, gal-13, gal-14, and gal-16, highlighting their shared and unique roles in maternal and placental immune regulation and placental development. Additionally, the review explores the potential of maternal versus placental galectins as biomarkers and therapeutic targets to improve diagnostic and treatment strategies for adverse pregnancy outcomes.<\/jats:p>","DOI":"10.1007\/s00281-025-01061-w","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:54:43Z","timestamp":1755766483000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Maternal and placental galectins: key players in the feto-maternal symbiotic tango"],"prefix":"10.1007","volume":"47","author":[{"given":"Orsolya","family":"Oravecz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Balogh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1t\u00e9","family":"Posta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Harms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emese","family":"Farkas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Borowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia","family":"Szekeres-Barth\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9385-7019","authenticated-orcid":false,"given":"N\u00e1ndor G\u00e1bor","family":"Than","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-2660","authenticated-orcid":false,"given":"Sandra M.","family":"Blois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"1061_CR1","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1146\/annurev-immunol-041015-055402","volume":"34","author":"S Thiemann","year":"2016","unstructured":"Thiemann S, Baum LG (2016) Galectins and immune responses-just how do they do those things they do? 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