{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:28:53Z","timestamp":1768523333656,"version":"3.49.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"OHSU University Shared Resources Pilot"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HG010333"],"award-info":[{"award-number":["R01HG010333"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24HG012483"],"award-info":[{"award-number":["U24HG012483"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD078641"],"award-info":[{"award-number":["R01HD078641"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50HD096723"],"award-info":[{"award-number":["P50HD096723"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health Office of Directors","award":["P51 OD011092"],"award-info":[{"award-number":["P51 OD011092"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potentially leading to male infertility. Recent research has rapidly increased the number of coding mutations causally linked to impaired spermatogenesis in humans and mice. However, the role of noncoding mutations remains largely unexplored. To evaluate the effects of noncoding mutations on spermatogenesis, we first identified an evolutionarily conserved topologically associated domain boundary near two genes with important roles in mammalian testis function: Dmrtb1 and Lrp8. We then used CRISPR-Cas9 to generate a mouse line where 26\u00a0kb of the boundary was removed including a strong and evolutionarily conserved CTCF binding site. ChIP-seq and Hi-C experiments confirmed the removal of the CTCF site and a resulting mild increase in the DNA\u2013DNA interactions across the domain boundary. Mutant mice displayed significant changes in testis gene expression, a higher frequency of histological abnormalities, a drop of 47\u201352% in efficiency of meiosis, a 15\u201318% reduction in efficiency of spermatogenesis, and, consistently, a 12\u201328% decrease in daily sperm production compared to littermate controls. Despite these quantitative changes in testis function, mutant mice show no significant changes in fertility. This suggests that noncoding deletions affecting testis gene regulation may have smaller effects on fertility compared to coding mutations of the same genes. Our results demonstrate that disruption of a topologically associated domain boundary can have a negative impact on sperm production and highlight the importance of considering noncoding mutations in the analysis of patients with male infertility.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf017","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T18:01:26Z","timestamp":1738692086000},"page":"767-779","source":"Crossref","is-referenced-by-count":5,"title":["Deletion of an evolutionarily conserved TAD boundary impacts spermatogenesis in mice"],"prefix":"10.1093","volume":"112","author":[{"given":"Ana C","family":"Lima","sequence":"first","affiliation":[{"name":"Division of Genetics, Oregon National Primate Research Center , 505 NW 185th Avenue, Beaverton, OR 97006 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariam","family":"Okhovat","sequence":"additional","affiliation":[{"name":"Department of Medicine, Knight Cardiovascular Institute, Oregon Health & Science University , 3181 SW Sam Jackson Rd, Portland, OR 97239 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra M","family":"Stendahl","sequence":"additional","affiliation":[{"name":"Division of Genetics, Oregon National Primate Research Center , 505 NW 185th Avenue, Beaverton, OR 97006 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Genetics, Oregon National Primate Research Center , 505 NW 185th Avenue, Beaverton, OR 97006 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jake","family":"VanCampen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Knight Cardiovascular Institute, Oregon Health & Science University , 3181 SW Sam Jackson Rd, Portland, OR 97239 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Francisco , 513 Parnassus Ave, San Francisco, CA 9414 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana","family":"Harshman","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco , UCSF Box 0775, 1700 Fourth St Rm 216D, San Francisco, CA 94143 ,","place":["USA"]},{"name":"Institute for Human Genetics, University of California San Francisco , 513 Parnassus Ave, San Francisco, CA 9414 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lev M","family":"Fedorov","sequence":"additional","affiliation":[{"name":"OHSU Transgenic Mouse Models Core Lab, Oregon Health & Science University , 3181 SW Sam Jackson Park Road, Portland, OR 97239 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katinka A","family":"Vigh-Conrad","sequence":"additional","affiliation":[{"name":"Division of Genetics, Oregon National Primate Research Center , 505 NW 185th Avenue, Beaverton, OR 97006 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadav","family":"Ahituv","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco , UCSF Box 0775, 1700 Fourth St Rm 216D, San Francisco, CA 94143 ,","place":["USA"]},{"name":"Institute for Human Genetics, University of California San Francisco , 513 Parnassus Ave, San Francisco, CA 9414 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald F","family":"Conrad","sequence":"additional","affiliation":[{"name":"Division of Genetics, Oregon National Primate Research Center , 505 NW 185th Avenue, Beaverton, OR 97006 ,","place":["USA"]},{"name":"Department of Molecular and Medical Genetics, Oregon Health & Science University , 3222 SW Research Drive, Mail Code: L103, Portland, OR 97239 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