{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:39:53Z","timestamp":1770493193912,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["3\/1\/2\/1\/15\/RCH"],"award-info":[{"award-number":["3\/1\/2\/1\/15\/RCH"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["SERB\u2010JCB\/2017\/000027"],"award-info":[{"award-number":["SERB\u2010JCB\/2017\/000027"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Infertility has become a global phenomenon and constantly declining sperm count in males in modern world pose a major threat to procreation of humans. Male fertility is critically dependent on proper functioning of testicular Sertoli cells. Defective Sertoli cell proliferation and\/or impaired functional maturation may be one of the underlying causes of idiopathic male infertility. Using high\u2010throughput \u201comics\u201d approach, we\u00a0found\u00a0binding sites for homeobox transcription factor MEIS1 on the promoters of several genes up\u2010regulated in pubertal (mature) Sertoli cells, indicating that MEIS1 may be\u00a0crucial\u00a0for Sertoli cell\u2010mediated regulation of spermatogenesis at and after puberty.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To decipher the role of transcription factor MEIS1 in Sertoli cell maturation and spermatogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Sc\u2010specific <jats:italic>Meis1<\/jats:italic> knockdown (KD) transgenic mice were generated using pronuclear microinjection. Morphometric and histological analysis of the testes from transgenic mice was performed to identify defects in spermatogenesis. Epididymal sperm count and litter size were analyzed to determine the effect of Meis1 knockdown on fertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sertoli cell (Sc)\u2010specific <jats:italic>Meis1<\/jats:italic> KD led to massive germ cell loss due to apoptosis and impaired spermatogenesis. Unlike normal pubertal Sc, the levels of SOX9 in pubertal Sc of <jats:italic>Meis1<\/jats:italic> KD were significantly high, like immature Sc. A significant reduction in epididymal sperm count was observed in these mice. The mice were found to be infertile or sub\u2010fertile (with reduced litter size), depending on the extent of <jats:italic>Meis1<\/jats:italic> inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results of this study demonstrated for the first time, a role of <jats:italic>Meis1<\/jats:italic> in Sc maturation and normal spermatogenic progression. Inhibition of <jats:italic>Meis1<\/jats:italic> in Sc was associated with deregulated spermatogenesis and a consequent decline in fertility of the transgenic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results provided substantial evidence that suboptimal <jats:italic>Meis1<\/jats:italic> expression in Sc may be one of the underlying causes of idiopathic infertility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12941","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T09:04:43Z","timestamp":1604480683000},"page":"689-699","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Homeobox transcription factor Meis1 is crucial to Sertoli cell mediated regulation of male fertility"],"prefix":"10.1111","volume":"9","author":[{"given":"Rajesh K.","family":"Sarkar","sequence":"first","affiliation":[{"name":"Cellular Endocrinology Lab National Institute 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