{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:24:24Z","timestamp":1790958264184,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J01681"],"award-info":[{"award-number":["2021J01681"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cryptorchidism, characterized by the failure of one or both testes to descend into the scrotum, is a common congenital condition that can lead to infertility and increased risk of testicular cancer.\n                      <jats:italic>CCDC149<\/jats:italic>\n                      , a coiled\u2010coil domain\u2010containing protein, has been implicated in various developmental processes, but its role in the male reproductive system remains unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aims to investigate the role of\n                      <jats:italic>CCDC149<\/jats:italic>\n                      mutations in the development of bilateral cryptorchidism and to elucidate the underlying molecular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      We conducted a whole\u2010exome sequencing of an 8\u2010year\u2010old boy diagnosed with bilateral cryptorchidism, revealing a mutation in the\n                      <jats:italic>CCDC149<\/jats:italic>\n                      gene. To further explore the functional implications of this mutation, we utilized CRISPR\/Cas9 technology to generate\n                      <jats:italic>Ccdc149<\/jats:italic>\n                      knockout mice. The phenotypic characteristics of these mice were assessed, focusing on testicular descent and sperm morphology. Additionally, single\u2010cell RNA sequencing was performed to analyze the expression of genes associated with\n                      <jats:italic>CCDC149<\/jats:italic>\n                      , including anti\u2010M\u00fcllerian hormone (\n                      <jats:italic>AMH<\/jats:italic>\n                      ) and muscle\u2010related factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>Ccdc149<\/jats:italic>\n                      knockout mice exhibited significant phenotypic traits consistent with cryptorchidism, including undescended testes and oligoasthenoteratozoospermia. Single\u2010cell RNA sequencing analysis revealed altered expression patterns of\n                      <jats:italic>AMH<\/jats:italic>\n                      and several muscle\u2010related genes, suggesting a potential regulatory interaction between CCDC149,\n                      <jats:italic>AMH<\/jats:italic>\n                      , and muscle development factors in the context of testicular descent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings provide novel genetic insights into the role of\n                      <jats:italic>CCDC149<\/jats:italic>\n                      mutations in cryptorchidism. The observed phenotypic characteristics in the knockout mice, along with the gene expression analysis, indicate that\n                      <jats:italic>CCDC149<\/jats:italic>\n                      may be crucial for normal testicular descent through its interaction with\n                      <jats:italic>AMH<\/jats:italic>\n                      and muscle\u2010related factors. These results highlight the importance of further research into the molecular mechanisms underlying cryptorchidism, which could lead to improved diagnostic and therapeutic strategies for affected individuals.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70072","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T08:35:05Z","timestamp":1748939705000},"page":"1155-1163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cryptorchidism: Novel genetic insights into\n                    <i>CCDC149<\/i>\n                    mutations"],"prefix":"10.1111","volume":"14","author":[{"given":"Shengrong","family":"Du","sequence":"first","affiliation":[{"name":"Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University School of Basic Medical Sciences Fujian Medical University  Fuzhou Fujian China"},{"name":"Center of Reproductive Medicine Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics &amp; Gynecology and Pediatrics Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Xu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Innate Immune Biology Biomedical Research Center of South China College of Life Sciences Fujian Normal University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics &amp; Gynecology and Pediatrics Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ye","sequence":"additional","affiliation":[{"name":"Ganzhou Key Laboratory of Molecular Medicine the Affiliated Ganzhou Hospital of Nanchang University  Ganzhou Jiangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University School of Basic Medical Sciences Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyun","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University School of Basic Medical Sciences Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqing","family":"Dong","sequence":"additional","affiliation":[{"name":"The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Yao","sequence":"additional","affiliation":[{"name":"Nanchang Reproductive Hospital Jiangxi University of Chinese Medicine Affiliated Reproductive Hospital Andrology  Nanchang Jiangxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Engineering and Regenerative Medicine of Fujian Province University School of Basic Medical Sciences Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00906"},{"key":"e_1_2_9_3_1","unstructured":"LeslieSW SajjadH VillanuevaCA.Cryptorchidism.StatPearls;2024."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.13247"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild\u20102012\u2010302051"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2016.08.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radcr.2022.10.022"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem\u20102015\u20100098"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067588"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20104642(18)30254\u20102"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012\u20101089"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.18.2.0298"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008\u20100358"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP\u201006\u20100272"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2017.90"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2015.00152"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018\u201000140"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200398200"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102019\u2010106203"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.19.2309"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2022.101619"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.108969"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD09260"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00596"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42000\u2010024\u201000546\u2010x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv313"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-021-00595-2"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.116.141408"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69160"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006469"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2022.847481"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2022.0389"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.045"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(85)92739\u20104"},{"key":"e_1_2_9_35_1","first-page":"734","article-title":"Role of the testis in the regulation of testicular descent","volume":"17","author":"Baumans V","year":"1981","journal-title":"Israel J Med Sci"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2020.01.016"},{"key":"e_1_2_9_37_1","volume-title":"Larsen's human embryology","author":"Schoenwolf GC","year":"2014"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012\u20101089"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP\u201006\u20100272"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20105347(17)41998\u20107"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20105347(17)50507\u20108"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20105347(17)45972\u20106"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1677\u20105538.IBJU.2024.9914"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2010.11.892"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2021.05.007"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2017.05.021"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2021.08.017"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70072","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.70072","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:55:04Z","timestamp":1783925704000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.70072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,3]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/andr.70072"],"URL":"https:\/\/doi.org\/10.1111\/andr.70072","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,3]]},"assertion":[{"value":"2024-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}