{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T21:24:50Z","timestamp":1785533090625,"version":"3.56.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The testis is a key reservoir of long non\u2010coding RNAs, yet their physiological roles in male reproduction remain debated. Notably, long non\u2010coding RNAs <jats:italic>1700101O22Rik<\/jats:italic> (<jats:italic>22Rik<\/jats:italic>) and <jats:italic>1700027A15Rik<\/jats:italic> (<jats:italic>15Rik<\/jats:italic>) are uniquely expressed in the mouse testis. Previous research indicates that both <jats:italic>22Rik<\/jats:italic> and <jats:italic>15Rik<\/jats:italic> play roles in male reproductive processes; however, it is still unclear whether their effects on fertility are cumulative or compensatory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the influence of simultaneous deletion of <jats:italic>22Rik<\/jats:italic> and <jats:italic>15Rik<\/jats:italic> on male reproduction and whether there are additive effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p><jats:italic>22Rik<\/jats:italic> and <jats:italic>15Rik<\/jats:italic> knockout mice were generated using CRISPR\u2010Cas9, and double knockout mice were obtained through co\u2010caging. To investigate reproductive phenotypes, we utilized computer\u2010aided sperm analysis, acrosome reaction assessments, in vitro fertilization techniques, and sperm morphology analysis. Additionally, RNA sequencing and RNA binding protein immunoprecipitation were employed to explore the regulatory mechanisms of <jats:italic>22Rik<\/jats:italic> and <jats:italic>15Rik<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The simultaneous deletion of <jats:italic>22Rik<\/jats:italic> and <jats:italic>15Rik<\/jats:italic> led to abnormal sperm morphology, impaired acrosome reaction, and reduced in vitro fertilization. Sperm count and fertility were also decreased in double knockout male mice. Compared to the knockout of long non\u2010coding RNA <jats:italic>22Rik<\/jats:italic>, reproductive abnormalities were somewhat exacerbated but largely similar to those observed with <jats:italic>15Rik<\/jats:italic> knockout alone because of shared targeted genes, particularly Y chromosome\u2010linked genes. Additionally, these abnormal phenotypes may be linked to reduced expression of transition protein 1 and dysfunction of the HSF2\u2012<jats:italic>Rik22<\/jats:italic>\u2012<jats:italic>Rik15<\/jats:italic> complex in double knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>Our study demonstrates for the first time that simultaneous knockout of these two long non\u2010coding RNAs adversely affects sperm morphology and function by disrupting the HSF2\u2012<jats:italic>Rik22<\/jats:italic>\u2012<jats:italic>Rik15<\/jats:italic> complex. Moreover, many overlapping regulated genes suggest that <jats:italic>22Rik<\/jats:italic> and <jats:italic>15Rik<\/jats:italic> may share similar regulatory mechanisms at the molecular level. This research sheds light on the causes and mechanisms behind sperm malformation and impaired male fertility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.70011","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T12:30:17Z","timestamp":1739536217000},"page":"1223-1235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Loss of lncRNAs 1700101O22Rik and 1700027A15Rik causes sperm malformation and subfertility"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3040-5979","authenticated-orcid":false,"given":"Shijue","family":"Dong","sequence":"first","affiliation":[{"name":"Institute of Reproductive Medicine Medical School Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Medicine Medical School Nantong 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