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However, xenografted testis of human and most endangered species are known to undergo spermatogenic arrest. In this study, we xenografted immature rat testis onto immunodeficient male mice to investigate the plausible underlying causes of spermatogenic arrest. Histological analysis of xenografted testes collected 8-wk post-grafting showed incomplete spermatogenesis with pachytene-stage spermatocytes as the most advanced germ cells. Although the levels of serum luteinizing hormone and testosterone were normal in recipient mice, those of follicle stimulating hormone (FSH) were significantly high, and specific receptors of FSH were absent in the xenografts. The xenografts demonstrated dysregulated expression of Sertoli cell-transcriptional regulators (WT1 and SOX9) and secretory proteins (SCF and GDNF). In conclusion, results from our study suggested that an altered hormonal milieu in recipients and dysregulated protein expression in xenografts could be a potential cause of spermatogenic arrest in xenografted immature rat testis. Further stereological analysis of xenografts can demonstrate precise cellular composition of xenografts to decipher interactions between germ and somatic cells to better understand spermatogenic arrest in xenografted testis.<\/jats:p>","DOI":"10.1038\/s41598-019-40662-y","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T11:02:58Z","timestamp":1552302178000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Altered hormonal milieu and dysregulated protein expression can cause spermatogenic arrest in ectopic xenografted immature rat testis"],"prefix":"10.1038","volume":"9","author":[{"given":"Sandeep","family":"Goel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naojiro","family":"Minami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,11]]},"reference":[{"key":"40662_CR1","doi-asserted-by":"publisher","first-page":"R71","DOI":"10.1530\/REP-14-0249","volume":"148","author":"L Arregui","year":"2014","unstructured":"Arregui, L. & Dobrinski, I. Xenografting of testicular tissue pieces: 12 years of an in vivo spermatogenesis system. Reproduction 148, R71\u2013R84, https:\/\/doi.org\/10.1530\/REP-14-0249 (2014).","journal-title":"Reproduction"},{"key":"40662_CR2","doi-asserted-by":"publisher","first-page":"3039","DOI":"10.1093\/humrep\/17.12.3039","volume":"17","author":"T Shinohara","year":"2002","unstructured":"Shinohara, T. et al. Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination. Human reproduction 17, 3039\u20133045 (2002).","journal-title":"Human reproduction"},{"key":"40662_CR3","doi-asserted-by":"publisher","first-page":"e70989","DOI":"10.1371\/journal.pone.0070989","volume":"8","author":"H Kaneko","year":"2013","unstructured":"Kaneko, H. et al. Generation of live piglets for the first time using sperm retrieved from immature testicular tissue cryopreserved and grafted into nude mice. 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