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In this study, we have demonstrated unequivocally that a functional and intact BTB is crucial for the initiation of spermatogenesis, in particular, the differentiation of spermatogonial stem cells (SSCs). It was shown that adult rats (\u223c300\u2003g body weight, b.w.) treated with adjudin at 50 (low\u2010dose) or 250 (high\u2010dose)\u2003mg\/kg b.w. by gavage led to germ\u2010cell depletion from the seminiferous tubules and that &gt;98% of the tubules were devoid of germ cells by \u223c2\u2003week and rats became infertile in both groups after the sperm reserve in the epididymis was exhausted. While the population of SSC\/spermatogonia in the seminiferous tubules from both groups was similar to that of normal rats, only rats from the low\u2010dose group were capable of re\u2010initiating spermatogenesis; and by 20 weeks, greater than 75% of the tubules displayed normal spermatogenesis and the fertility of these rats rebounded. Detailed analysis by dual\u2010labelled immunofluorescence analysis and a functional BTB integrity assay revealed that in both treatment groups, the BTB was disrupted from week 6 to week 12. However, the disrupted BTB \u2018resealed\u2019 in the low\u2010dose group, but not in the high\u2010dose group. Our findings illustrate that SSC\/spermatogonia failed to differentiate into spermatocytes beyond A<jats:sub>aligned<\/jats:sub> spermatogonia in the high\u2010dose group with a disrupted BTB. In short, these findings illustrate the critical significance of the BTB for <jats:italic>re\u2010initiation<\/jats:italic> of spermatogenesis besides SSC and spermatogonia.<\/jats:p>","DOI":"10.1111\/j.1365-2605.2011.01183.x","type":"journal-article","created":{"date-parts":[[2011,6,23]],"date-time":"2011-06-23T01:40:21Z","timestamp":1308793221000},"page":"86-101","source":"Crossref","is-referenced-by-count":53,"title":["Spermatogonial stem cells alone are not sufficient to re\u2010initiate spermatogenesis in the rat testis following adjudin\u2010induced infertility"],"prefix":"10.1111","volume":"35","author":[{"given":"K\u2010W.","family":"Mok","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. D.","family":"Mruk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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