{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:01:41Z","timestamp":1792040501137,"version":"4.4.0"},"reference-count":123,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T00:00:00Z","timestamp":1687564800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R21HD110878"],"award-info":[{"award-number":["R21HD110878"]}]},{"name":"Green Center for Reproductive Biology Endowment"},{"name":"UT Southwestern Medical Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Mammalian reproduction requires the fusion of two specialized cells: an oocyte and a sperm. In addition to producing gametes, the reproductive system also provides the environment for the appropriate development of the embryo. Deciphering the reproductive system requires understanding the functions of each cell type and cell\u2013cell interactions. Recent single-cell omics technologies have provided insights into the gene regulatory network in discrete cellular populations of both the male and female reproductive systems. However, these approaches cannot examine how the cellular states of the gametes or embryos are regulated through their interactions with neighboring somatic cells in the native tissue environment owing to tissue disassociations. Emerging spatial omics technologies address this challenge by preserving the spatial context of the cells to be profiled. These technologies hold the potential to revolutionize our understanding of mammalian reproduction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>OBJECTIVE AND RATIONALE<\/jats:title>\n                  <jats:p>We aim to review the state-of-the-art spatial transcriptomics (ST) technologies with a focus on highlighting the novel biological insights that they have helped to reveal about the mammalian reproductive systems in the context of gametogenesis, embryogenesis, and reproductive pathologies. We also aim to discuss the current challenges of applying ST technologies in reproductive research and provide a sneak peek at what the field of spatial omics can offer for the reproduction community in the years to come.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SEARCH METHODS<\/jats:title>\n                  <jats:p>The PubMed database was used in the search for peer-reviewed research articles and reviews using combinations of the following terms: \u2018spatial omics\u2019, \u2018fertility\u2019, \u2018reproduction\u2019, \u2018gametogenesis\u2019, \u2018embryogenesis\u2019, \u2018reproductive cancer\u2019, \u2018spatial transcriptomics\u2019, \u2018spermatogenesis\u2019, \u2018ovary\u2019, \u2018uterus\u2019, \u2018cervix\u2019, \u2018testis\u2019, and other keywords related to the subject area. All relevant publications until April 2023 were critically evaluated and discussed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>OUTCOMES<\/jats:title>\n                  <jats:p>First, an overview of the ST technologies that have been applied to studying the reproductive systems was provided. The basic design principles and the advantages and limitations of these technologies were discussed and tabulated to serve as a guide for researchers to choose the best-suited technologies for their own research. Second, novel biological insights into mammalian reproduction, especially human reproduction revealed by ST analyses, were comprehensively reviewed. Three major themes were discussed. The first theme focuses on genes with non-random spatial expression patterns with specialized functions in multiple reproductive systems; The second theme centers around functionally interacting cell types which are often found to be spatially clustered in the reproductive tissues; and the thrid theme discusses pathological states in reproductive systems which are often associated with unique cellular microenvironments. Finally, current experimental and computational challenges of applying ST technologies to studying mammalian reproduction were highlighted, and potential solutions to tackle these challenges were provided. Future directions in the development of spatial omics technologies and how they will benefit the field of human reproduction were discussed, including the capture of cellular and tissue dynamics, multi-modal molecular profiling, and spatial characterization of gene perturbations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS<\/jats:title>\n                  <jats:p>Like single-cell technologies, spatial omics technologies hold tremendous potential for providing significant and novel insights into mammalian reproduction. Our review summarizes these novel biological insights that ST technologies have provided while shedding light on what is yet to come. Our review provides reproductive biologists and clinicians with a much-needed update on the state of art of ST technologies. It may also facilitate the adoption of cutting-edge spatial technologies in both basic and clinical reproductive research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humupd\/dmad017","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T23:17:44Z","timestamp":1687648664000},"page":"794-810","source":"Crossref","is-referenced-by-count":24,"title":["Dissecting mammalian reproduction with spatial transcriptomics"],"prefix":"10.1093","volume":"29","author":[{"given":"Xin","family":"Zhang","sequence":"first","affiliation":[{"name":"Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center , Dallas, TX, USA"},{"name":"Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center , Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Cao","sequence":"additional","affiliation":[{"name":"Cecil H. and Ida Green Center for 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