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Administered ip 1 h prior to local testicular heating. Additional groups of 5 mice received an ip injection of vehicle or minocycline and served as controls. Animal handling and experimentation were in accordance with the recommendation of the American Veterinary Medical Association and were approved by the Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute animal care and use review committee. Tissue Preparation Both control and experimental animals were injected with heparin 130 IU 100 g BW, ip ; 15 min before a lethal injection of sodium pentobarbital 100 mg kg BW, ip ; to facilitate testicular perfusion using a whole body perfusion technique [21]. After perfusion with saline, one testis was removed, decapsulated, weighed, snap frozen in liquid N2, and stored at -70C for subsequent analysis. The contralateral testes were then fixed by vascular perfusion with either 5% glutaraldehyde in 0.05M cacodylate buffer pH 7.4 ; or Bouin's solution Sigma Diagnostics, St. Louis, MO ; . The testes were removed and processed for routine paraffin embedding for either in situ detection of apoptosis or immunohistochemistry. Portions of glutaraldehyde-fixed testes were further diced into small pieces, post-fixed into 1% osmium tetroxide, and embedded in Epon 812 Polysciences, Warrington, PA ; . Thin sections from selected tissue blocks were cut with an LKB ultramicrotome, stained with uranyl acetate and lead citrate, and examined with a Hitachi 600 electron microscope. Assessment of apoptosis In situ detection of cells with DNA strand breaks was performed in glutaraldehyde-fixed, paraffin-embedded testicular sections by the terminal deoxynucleotidyl transferase and zestoretic.

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