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These evolutionary patterns are thought to be a consequence of rapid divergence in gene expression driven by maternal\u2013fetal conflict over resource allocation. However, it remains unclear how the diversity of placental functions shapes gene specialization and expression divergence. We generated genome-wide gene expression and DNA methylation data from fetal and maternal placental tissues of three closely related mouse lineages (Mus musculus musculus, M.\u2019m.\u2019domesticus, M. spretus) and integrated single-cell expression data to investigate how tissue specialization influences gene expression evolution in the rodent placenta. Comparisons among placental regions within M.\u2019m.\u2019musculus revealed significant differences in patterns of functional enrichment, imprinting, and X-linked expression across placental layers. The labyrinth zone, the primary site of nutrient exchange, showed strong enrichment for parent-of-origin expression of both autosomal and X-linked genes. Cross-species comparisons of gene expression within each placental layer revealed increased expression level divergence at the maternal\u2013fetal interface. We also identified a subset of genes with maternally biased expression that are spatially associated with the maternal\u2013fetal interface. Parent-of-origin DNA methylation was dominated by epigenetic modification of the maternal genome and interspecific comparisons of parent-of-origin expression revealed overall conservation punctuated by changes in imprinting status of two genes. These findings unveil important links between core elements of placental biology and the evolution of placental gene expression, demonstrating how tissue specialization has influenced parent-of-origin effects and interspecific expression divergence.<\/jats:p>","DOI":"10.1093\/gbe\/evag120","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:39:23Z","timestamp":1779190763000},"source":"Crossref","is-referenced-by-count":0,"title":["Evolution of Gene Expression Across Functional Regions of the Mouse Placenta"],"prefix":"10.1093","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-2095","authenticated-orcid":false,"given":"Fernando","family":"Rodriguez-Caro","sequence":"first","affiliation":[{"name":"Division of Biological and Biomedical Sciences, The University of Montana , Missoula, MT 59812 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6166-3367","authenticated-orcid":false,"given":"Emily C","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, The University of Montana , Missoula, MT 59812 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6626-5831","authenticated-orcid":false,"given":"Ashlin","family":"Slanger","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, The University of Montana , Missoula, MT 59812 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0707-5374","authenticated-orcid":false,"given":"Jeffrey M","family":"Good","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, The University of Montana , Missoula, MT 59812 , 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