title: Spermatogonial stem cells alone are not sufficient to re-initiate spermatogenesis in the rat testis following adjudin-induced infertility.
abstract: The blood-testis barrier (BTB) is a unique ultrastructure in the testis, which creates a specialized microenvironment in the seminiferous epithelium known as the apical (or adluminal) compartment for post-meiotic germ-cell development and for maintenance of an immunological barrier. 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 (∼300 g body weight, b.w.) treated with adjudin at 50 (low-dose) or 250 (high-dose) mg/kg b.w. by gavage led to germ-cell depletion from the seminiferous tubules and that >98% of the tubules were devoid of germ cells by ∼2 week 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-dose group were capable of re-initiating 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-labelled 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 'resealed' in the low-dose group, but not in the high-dose group. Our findings illustrate that SSC/spermatogonia failed to differentiate into spermatocytes beyond A(aligned) spermatogonia in the high-dose group with a disrupted BTB. In short, these findings illustrate the critical significance of the BTB for re-initiation of spermatogenesis besides SSC and spermatogonia.
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: K-W
authors.initials: KW
authors.lastname: Mok
authors.forename: D D
authors.initials: DD
authors.lastname: Mruk
authors.forename: W M
authors.initials: WM
authors.lastname: Lee
authors.forename: C Y
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000378:metabolism*; D007191:Indazoles / Q000378:metabolism*; D008297:Male; D051381:Rats; D013091:Spermatogenesis; D013093:Spermatogonia / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*
chemical_list: C432482:1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; D006834:Hydrazines; D007191:Indazoles